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Chapter 2

Health effects of exposure to secondhand smoke


(SHS)

Introduction

In this chapter the Working Group on local circumstances, particularly This chapter briefly reviews the
summarises the major reviews that the prevalence of exposure. findings of the various reports on
have been conducted in the last the consequences of exposure to
10 years on the health effects of Non-malignant effects of SHS SHS (Table 2.1). The many adverse
secondhand smoke (SHS). Where exposure effects of SHS, beyond the causation
substantial new studies have been of cancer, strengthen the rationale for
reported in the last few years, we Overview achieving smoke-free environments,
describe these also, but do not including not only public and
attempt a formal assessment of the Exposure to SHS adversely affects workplaces, but homes, so as to
evidence overall. First, the literature the health of children and adults ensure that children are protected
on the relation between SHS and (Table 2.1). The inhalation of this from exposure to SHS. The most
cardiovascular diseases is reviewed, mixture of irritant, toxic particles, and recent reports, particularly the 2005
since these conditions, and acute gases has respiratory effects, as well California Environmental Protection
myocardial infarction (AMI) in as effects on other organ systems, Agency (EPA) report and the 2006
particular, are leading contributors including causing coronary heart report of the US Surgeon General,
to the burden of disease caused disease (CHD) in adults and sudden provide comprehensive coverage
by SHS. The chapter then provides infant death syndrome (SIDS) in of the epidemiological evidence
an overview of effects of SHS on infants. There has been extensive and relevant research findings
respiratory conditions and child research on mechanisms by which related to the plausibility of causal
health. Lastly, the link between SHS SHS causes these adverse effects; associations of SHS with respiratory
and cancer is examined, including that evidence has been most recently and cardiovascular effects.
the accumulation of evidence over reviewed in the 2006 report of the US Beyond these adverse health
time, and what is known about Surgeon General and is not covered effects, tobacco smoke, which
the relationship with cancers at specifically in this chapter. However, contains numerous irritants, has long
particular sites. The emphasis in this we note the evidence was sufficient been linked to odor and annoyance
chapter lies on the already answered to support a major conclusion of this (U.S. Department of Health and
question of whether SHS is a cause report, that “[c]hildren exposed to Human Services, 1986). Both ques-
of disease, and if so, what is the secondhand smoke are at increased tionnaire surveys and laboratory
relation between level of exposure risk for sudden infant death syndrome studies, involving exposure to SHS,
and risk of disease. However, briefly (SIDS), acute respiratory infections, have shown annoyance and irritation
we consider the related question of ear problems and more severe of the eyes and upper and lower
how much ill health may be attributed asthma. Smoking by parents causes airways from involuntary smoking.
to exposures to SHS. This quantity, respiratory symptoms and slows In several surveys of nonsmokers,
the burden of disease due to SHS, lung growth in their children” (U.S. complaints about tobacco smoke
may be an important consideration for Department of Health and Human at work and in public places were
policy-makers and depends heavily Services, 2006). common (U.S. Department of Health

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IARC Handbooks of Cancer Prevention

Table 2.1 Adverse effects from exposure to tobacco smoke published in major reports

UK
SGR SGR EPA Cal EPA WHO IARC Cal EPA* SGR
Health effect 1998/
1984 1986 1992 1997 1999 2004 2005** 2006
2004

Increased prevalence of
Yes/a Yes/a Yes/c Yes/c Yes/c Yes/c Yes/c Yes/c
Chronic respiratory symptoms

Decrement in pulmonary
Yes/a Yes/a Yes/a Yes/a Yes/a* Yes/c Yes/a Yes/c
function

Increased occurrence of
Yes/a Yes/a Yes/a Yes/c Yes/c Yes/c Yes/c
acute respiratory illnesses

Increased occurrence of
Yes/a Yes/c Yes/c Yes/c Yes/c Yes/c Yes/c
middle ear disease

Increased severity of asthma


Yes/c Yes/c Yes/c Yes/c Yes/c
episodes and symptoms

Risk factor for new asthma Yes/a Yes/c Yes/c Yes/c

Risk factor for SIDS Yes/c Yes/a Yes/c Yes/c Yes/c

Risk factor for lung cancer in


Yes/c Yes/c Yes/c Yes/c Yes/c Yes/c Yes/c
adults

Risk factor for breast cancer


for younger, primarily Yes/c
premenopausal women

Risk factor for nasal sinus


Yes/c
cancer

Risk factor for coronary heart


Yes/c Yes/c Yes/c Yes/c
disease in adults

SGR: US Surgeon General’s report; EPA: US Environmental Protection Agency; Cal EPA: California Environmental Protection Agency; WHO: World Health Organization; IARC:
International Agency for Research on Cancer; UK: United Kingdom Scientific Committee on Tobacco and Health
*Added in 2004
**Only effects causally associated with SHS exposure are included
Yes/a = association
Yes/c = cause
Table adapted from U.S. Department of Health and Human Services (2006) and from ASHRAE (Environmental Tobacco Smoke, position document, page 9, Table 1), (2005).
© American Society of Heating, Refrigerating and Air-Conditioning Engineers, Inc.

and Human Services, 1986). About the general level of exposure declines Childhood effects
50% of respondents complained (Junker et al., 2001). The odor and
about tobacco smoke at work, irritation associated with SHS merit Extensive epidemiological evidence
and a majority were disturbed by special consideration, because a has associated SHS exposure with
tobacco smoke in restaurants. The high proportion of nonsmokers are respiratory and non-respiratory dis-
experimental studies show that the annoyed by exposure to SHS, and eases and other adverse effects in
rate of eye blinking is increased by control of concentrations in indoor children. Since the first reports in
SHS, as are complaints of nose and air poses difficult problems in the the 1960s, studies from around the
throat irritation (U.S. Department of management of heating, ventilating, world have shown that smoking by
Health and Human Services, 1986). and air-conditioning systems. parents during pregnancy and after
One study suggests that there may the child’s birth causes disease,
be increasing sensitivity to SHS as resulting in premature mortality and

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Health effects of exposure to secondhand smoke (SHS)

substantial morbidity. Extensive data Board, 2005; U.S. Department of In 2005, the pathophysiological
on exposure, including measure- Health and Human Services, 2006). mechanisms by which SHS exposure
ments of SHS components in the might increase the risk of heart
air and of biomarkers, document Adulthood effects disease were summarised (Barnoya
the key role of smoking by parents & Glantz, 2005). They suggested
in exposing their children to SHS. Cardiovascular disease that passive smoking may promote
Studies have also addressed the atherogenesis; increase the ten-
mechanisms by which SHS causes The evidence indicating that SHS dency of platelets to aggregate,
its adverse effects. This evidence is causes CHD in adults has been and thereby promote thrombosis;
not reviewed in this chapter, as it has repeatedly reviewed since 1986. At impair endothelial cell function;
been recently reviewed in the reports that time, the US Surgeon General’s increase arterial stiffness leading to
of the California EPA and US Surgeon report examined one case-control atherosclerosis; reduce the oxygen-
General. study and three cohort studies carrying capacity of the blood; and
Table 2.1 lists the diseases on the association of involuntary alter myocardial metabolism, much as
and other adverse effects causally smoking and cardiovascular effects, for active smoking and CHD. Several
associated with exposure to SHS. concluding further research was separate experiments, involving
The list includes SIDS, an important needed to decide causality. A causal exposure of nonsmokers to SHS,
cause of death in children under a link between CHD and SHS was first have shown that passive smoking
year of age (Anderson & Cook, 1997); reported in the California EPA report affects measures of platelet function
acute lower respiratory illnesses, from 1997 (Table 2.1) in the direction of increased tendency
a major cause of morbidity and Causal associations between toward thrombosis (Glantz & Parmley,
mortality in children under five years active smoking and fatal and nonfatal 1995; Barnoya & Glantz, 2005). In
of age; and acute and chronic middle CHD outcomes have long been a 2004 study, sidestream smoke
ear disease, also a leading child demonstrated (U.S. Department of was found to be 50% more potent
health problem (U.S. Department of Health and Human Services, than mainstream smoke in activating
Health and Human Services, 2006). 2004). Active cigarette smoking is platelets (Rubenstein et al., 2004). It
SHS exposure worsens asthma and considered to increase the risk of was also proposed that carcinogenic
may contribute to its causation. It cardiovascular disease by promoting agents, such as polycyclic aromatic
also slows the rate of lung growth atherosclerosis; affecting endothelial hydrocarbons found in tobacco
during childhood and adolescence cell functioning; increasing the smoke, promote atherogenesis by
and is associated with increased tendency to thrombosis; causing effects on cell proliferation (Glantz &
prevalence of respiratory symptoms. spasm of the coronary arteries, Parmley, 1995). These mechanistic
The epidemiological evidence which increases the likelihood of considerations support both acute
on outcomes that have been cardiac arrhythmias; and decreasing and chronic effects of SHS exposure
causally linked to SHS exposure is the oxygen-carrying capacity of the on risk for cardiovascular disease.
substantial, and provides quantitative blood (U.S. Department of Health Exposure to SHS may also
estimates of the risk associated with and Human Services, 1990). These worsen the outcome of an ischemic
SHS. In general, risk increases with same mechanisms have been event in the heart: animal data have
the number of adult smokers in the considered to be relevant to SHS demonstrated that SHS exposure
household, and attributable risk exposure and risk for CHD (Barnoya increases cardiac damage following
estimates indicate that SHS exposure & Glantz, 2005; U.S. Department of an experimental myocardial infarc-
is a substantial contributor to the Health and Human Services, 2006). tion. Experiments on two species of
burden of respiratory morbidity in Experimental studies support the animals (rabbits and cockerels) have
childhood, as well as a major cause relevance of these mechanisms (U.S. demonstrated that not only does
of SIDS (California Environmental Department of Health and Human exposure to SHS at doses similar to
Protection Agency: Air Resources Services, 2006). exposure to humans accelerate the

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IARC Handbooks of Cancer Prevention

growth of atherosclerotic plaques geographically and racially. One studies (four case-control, two cohort,
through the increase of lipid deposits, group of studies addressed the and two cross-sectional) have been
but it also induces atherosclerosis. promotion of atherosclerosis and published exploring this association
There is also impressive and SHS exposure, using increased (Lee et al., 1986; Donnan et al.,
accumulating evidence that SHS carotid intimal-medial thickness 1989; Sandler et al., 1989; Howard
acutely affects vascular endothelial (IMT) as an indicator. These studies et al., 1998; Bonita et al., 1999; You
cell functioning (Celermajer et al., have shown both cross-sectional and et al., 1999; Zhang et al., 2005).
1996; Sumida et al., 1998; Otsuka et longitudinal associations of IMT with A large cross-sectional study of
al., 2001). Thirty minutes of exposure SHS exposure (Howard et al., 1994, 60 377 women in China, found an
to SHS in healthy young volunteers 1998; Diez-Roux et al., 1995). association between prevalent
was found to compromise coronary As the evidence since the first stroke in women and smoking by
artery endothelial function in a man- report has mounted, it has been their husbands (Zhang et al., 2005).
ner that was indistinguishable from reviewed systematically by the The prevalence of stroke increased
that of habitual smokers, suggesting American Heart Association (Taylor with greater duration of smoking
that endothelial dysfunction may be et al., 1992), the Australian National and with an increasing number of
an important mechanism by which Health and Medical Research Council cigarettes smoked daily. A cohort
exposure to SHS increases CHD risk (1997), the California EPA (California study was conducted of 19 035
(Otsuka et al., 2001). Environmental Protection Agency, lifetime nonsmokers using census
In addition to its effects on 1997; California Environmental data from Washington County, MD
platelets, SHS exposure affects Protection Agency: Air Resources (Sandler et al., 1989). Based on 297
the oxygen-carrying capacity of Board, 2005), the Scientific Committee cases among women exposed to
the blood through its carbon mon- on Tobacco and Health in the United SHS, a 24% increased risk of stroke
oxide component. Even small Kingdom (Scientific Committee on was found compared with those
increments, on the order of 1%, in the Tobacco and Health, 1998) and unexposed (95% CI=3-49%). Null
carboxyhemoglobin, may explain the most recently by the US Surgeon results were found for an association
finding that SHS exposure decreases General (U.S. Department of Health in men, but were limited to only 33
the duration of exercise of patients with and Human Services, 2006). Review cases. A case-control study in New
angina pectoris (Allred et al., 1989). of the evidence has uniformly led to Zealand, which looked at 265 cases
This is supported with evidence that the conclusion that there is a causal and 1336 controls, did find a two-
cigarette smoking has been shown to association between exposure to fold increased risk of stroke in men
increase levels of carbon monoxide in SHS and risk of cardiovascular exposed to SHS (Bonita et al., 1999).
the spaces where ventilation is low or disease (California Environmental Additionally, a 2004 prospective
smoking is particularly intense (U.S. Protection Agency , 1997; Scientific cohort study used serum cotinine
Department of Health and Human Committee on Tobacco and Health, levels for exposure classification
Services, 1986). 1998). The meta-analysis prepared (Whincup et al., 2004). The 20 year
A 1985 report, based on a cohort for the 2006 US Surgeon General’s study included 4729 men in the
study in southern California, was the report, estimated the pooled excess UK who provided baseline blood
first epidemiologic investigation to risk for coronary heart disease from samples in 1978 to 1980. A consistent
raise concerns that exposure to SHS SHS exposure from marriage to a association was not found between
may increase risk for CHD (Garland smoker as 27% (95% CI=19-36%) serum cotinine concentration and
et al., 1985). There are now more (U.S. Department of Health and stroke.
than 20 studies on the association Human Services, 2006).
between SHS and cardiovascular There is increasing epidemiologic Respiratory disease
disease, including cohort and evidence suggestive of a causal
case-control studies. They cover association between SHS exposure Exposure to SHS has been
a wide range of populations, both and stroke. At least eight epidemiologic explored as a contributing factor

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Health effects of exposure to secondhand smoke (SHS)

to respiratory morbidity in general, Welfare, 1972). That report reviewed ociation between exposure to SHS
including respiratory symptoms and the evidence on components of and lung cancer and the supporting
reduction of lung function, and also tobacco smoke in enclosed spaces epidemiological evidence (National
as a factor causing and exacerbating and commented on the potential Research Council, 1986). Based on a
both chronic obstructive pulmonary for inhaled pollutants from cigarette meta-analysis of the epidemiological
disease (COPD) and asthma. The smoke to cause disease. Beginning data adjusted for bias, the report
effects are plausible consequences of in the late 1960s, epidemiological concluded that the best estimate
exposure to SHS, given the evidence research addressed adverse effects for the excess risk of lung cancer
on active smoking and respiratory of smoking in the home on the in nonsmokers married to smokers
health, and knowledge of the health of children. In 1981, published was 25%. The 1986 report of the US
components and toxicity of SHS. To reports from Japan (Hirayama, Surgeon General also characterised
date, a range of adverse effects has 1981) and Greece (Trichopoulos et involuntary smoking as a cause of
been investigated. The evidence is al., 1981) indicated increased lung lung cancer in nonsmokers (U.S.
most consistent in showing that SHS cancer risk in nonsmoking women Department of Health and Human
exposure of adults may contribute to married to cigarette smokers. Services, 1986). This conclusion
respiratory symptoms, exacerbate These reports sparked a wave of was based on the extensive
underlying lung disease, and slightly additional epidemiological studies information already available on the
reduce lung function (Table 2.1). on lung cancer, as well as studies on carcinogenicity of active smoking, on
exposure to SHS, using biomarkers the qualitative similarities between
Secondhand smoke (SHS) and measurement of tobacco smoke SHS and mainstream smoke, and
and cancer components in indoor air. on the epidemiological data on
By 1986, the evidence had involuntary smoking.
Historical perspective mounted, and three reports published Subsequently, the many further
in that year concluded that SHS epidemiological studies on SHS and
The health effects of active smoking was a cause of lung cancer. In its lung cancer have better characterised
and the carcinogenicity of tobacco Monograph 38, IARC concluded the quantitative risk associated with
smoke became a focus of research that “passive smoking gives rise to SHS, and refined understanding of
in the first decades of the 20th some risk of cancer” (IARC, 1986). the doses of carcinogens received
century, as the first indications of the The IARC Working Group supported by nonsmokers who inhale it. Many
emerging lung cancer epidemic were this conclusion on the basis of the additional agencies have now
identified. By the 1950s, substantial characteristics of sidestream and concluded that SHS causes lung
epidemiological and experimental mainstream smoke, the absorption cancer and other diseases; adverse
research was in progress, leading of tobacco smoke materials during health effects have also been causally
to the conclusion in the 1960s that involuntary smoking, and the nature associated with SHS (Table 2.1). The
active smoking was a cause of lung of dose-response relationships for last IARC review on the topic of SHS
cancer (Royal College of Physicians carcinogenesis. In the same year, and cancer was in its Monograph
of London, 1962; U.S. Department of a US National Research Council 83, Tobacco Smoke and Involuntary
Health Education and Welfare, 1964). (NRC) committee (National Research Smoking, based on a Working Group
IARC published its first monograph Council, 1986) and the US Surgeon that convened in 2002 (IARC, 2004).
on tobacco smoking in 1986 (IARC, General (U.S. Department of Health The list of cancers investigated for
1986). and Human Services, 1986) also association with SHS is now lengthy,
The potential for tobacco smoke concluded that involuntary smoking with reports covering many of the
inhaled by nonsmokers to cause dis- increases the incidence of lung cancers caused by active smoking,
ease was first considered in the US cancer in nonsmokers. In reaching breast cancer, and childhood cancers.
Surgeon General’s report in 1972 (U.S. this conclusion, the NRC cited the The considerations around biological
Department of Health Education and biological plausibility of the ass- plausibility of a causal association of

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IARC Handbooks of Cancer Prevention

SHS exposure with these cancers, al., 2007). In preparing the evidence gioma, brain, head, neck, oral, nasal
reflect either local deposition of tables for this chapter, these sinus, nasopharyngeal, esophageal,
tobacco smoke components and reports provided a starting point lung, breast, kidney, stomach,
metabolites (sinonasal cancer and for identifying those studies that gastrointestinal, liver, pancreas,
gastrointestinal cancers) or their should be considered. Additionally, colon, colorectal, rectal, bladder,
systemic distribution (cancers of the literature searches were updated ovarian, prostate, and cervical
breast, bladder, pancreas, brain, using search strategies described cancer. Identified studies were
liver, and ovary, and leukemias and below. Quantitative summaries of screened and bibliographies were
lymphomas). the evidence were prepared when examined for related articles. Finally,
These conclusions on SHS and the data were sufficiently abundant publications of authors focusing on
disease risk have had substantial and with adequate homogeneity the field of smoking and cancer were
impact, providing a strong rationale of methodology and reporting of searched. The identified articles
for making public and workplaces findings. The method of DerSimonian were abstracted in a uniform fashion.
smoke-free. The significance of this and Laird was employed for this Data from never smokers were
research, and the related conclusions, pooling, using the statistical package presented in preference to data from
have motivated widespread efforts by Stata (DerSimonian & Laird, 1986). current or former smokers. When
the multinational tobacco companies Three major reports were the start- available, adjusted relative risks were
to discredit the scientific evidence ing point for the literature review on abstracted rather than crude results.
on SHS and disease, particularly the cancer: 1) The Health Consequences
findings of epidemiological studies of Involuntary Exposure to Tobacco Adult cancers
(Brandt, 2007). These efforts have Smoke: A Report of the Surgeon
now been documented through General (U.S. Department of Health Lung cancer
reviews of the industry’s internal and Human Services, 2006), 2)
documents, and these tactics were Proposed Identification of ETS as Overview
one element of the successful litigation a Toxic Air Contaminant (California
in the USA against the industry, Environmental Protection Agency: In numerous prior reports, including
which was found guilty of fraud and Air Resources Board, 2005), and IARC Monograph 83, the conclusion
racketeering (Kessler, 2006). 3) IARC Monograph 83: Tobacco has been reached that SHS causes
Smoke and Involuntary Smoking lung cancer in people who have never
Prior reviews and methods (IARC, 2004). The literature on SHS actively smoked (Table 2.1). The
for this review and cancer contained in these evidence has been found sufficient to
reports was systematically updated. infer causality based on the extensive
The evidence on SHS and cancer has A computerised literature search of evidence showing that active smok-
been serially reviewed. Reports have the electronic PubMed database ing causes lung cancer, the biological
been prepared by various agencies was conducted through December plausibility of a causal association
including most recently IARC in 31, 2007, without time or language of SHS with cancer risk, and the
2002 (IARC, 2004), the California restrictions. A keyword search consistency of the epidemiological
Environmental Protection Agency was performed on tobacco smoke findings. Alternative explanations to
in 2005 (California Environmental pollution, secondhand smoking, causation, particularly confounding
Protection Agency: Air Resources passive smoking, household smok- and information bias, have been
Board, 2005), and the US Surgeon ing, involuntary smoking, and en- repeatedly scrutinised and rejected.
General in 2006 (U.S. Department vironmental tobacco smoke, in A causal association of in-
of Health and Human Services, combination with cancer-related voluntary smoking with lung cancer
2006). Additionally, reports in peer- keywords. These keywords included derives biological plausibility from the
reviewed literature have addressed cancer, adenocarcinoma, lymphoma, presence of carcinogens in SHS and
the topic (Johnson, 2005; Taylor et leukemia, childhood, glioma, menin- the lack of a documented threshold

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Health effects of exposure to secondhand smoke (SHS)

dose for respiratory carcinogens in The epidemiological studies have less healthy lifestyle in those with
active smokers (U.S. Department primarily used self- or surrogate- greater SHS exposure (Matanoski
of Health and Human Services, report of exposure as the key indicator. et al., 1995). However, other than
1982, 1986, 2004; IARC, 1986). Marriage to a smoker, particularly a few occupational exposures at
Moreover, genotoxic activity has been for women, has been the most high levels, as well as indoor radon,
demonstrated for many components frequently used exposure indicator. risk factors for lung cancer in never
of SHS (Claxton et al., 1989; Lofroth, Methodological investigations sug- smokers that might confound the SHS
1989; Weiss, 1989; Bennett et al., 1999; gest that accurate information can association cannot be proffered, and
DeMarini, 2004). Experimental and be obtained by interview in an the relevance to past studies of these
real-world exposures of nonsmokers epidemiological study on the smoking current associations of potential
to SHS leads to their excreting 4-(N- habits of a spouse (i.e. never or ever confounders with SHS exposure is
methylnitrosamino)-1-(3-pyridyl)-1- smoker) (Pron et al., 1988; Coultas uncertain.
butanol (NNAL), a tobacco-specific et al., 1989; Cummings et al., 1989;
carcinogen, in their urine (Carmella et Lubin, 1999). However, information Epidemiological evidence
al., 2003; Hecht, 2003). Nonsmokers concerning quantitative aspects of
exposed to SHS also have increased the spouse’s smoking is reported The first major studies on SHS and
concentrations of adducts of tobacco- with less accuracy. Misclassification lung cancer were reported in 1981.
related carcinogens (Maclure et of current or former smokers as never Hirayama’s early report (Hirayama,
al., 1989; Crawford et al., 1994). smokers may introduce a positive 1981) was based on a prospective
Additionally, using an animal model, bias, because of the concordance of cohort study of 91 540 nonsmoking
researchers found that whole-body spouse smoking habits (Lee, 1998). women in Japan. Standardised mor-
exposure in rats to cigarette smoke The extent to which this bias explains tality ratios (SMRs) for lung cancer
increases the risk of neoplastic the numerous reports of association increased significantly with the
proliferative lung lesions and induces between spousal smoking and amount smoked by the husbands.
lung cancer (Mauderly et al., 2004). lung cancer has been addressed; The findings could not be explained
Time trends of lung cancer findings indicate that bias does not by confounding factors and were
mortality in nonsmokers have been account for the observed association unchanged when follow-up of the
examined, with the rationale that (Wald et al., 1986; Lee, 1988; U.S. study group was extended (Hirayama,
temporally increasing exposure Environmental Protection Agency, 1984). Based on the same cohort,
to SHS should be paralleled by 1992; Wu, 1999; U.S. Department of significantly increased risk was
increasing mortality rates (Enstrom, Health and Human Services, 2006). reported for nonsmoking men married
1979; Garfinkel, 1981). These data In some countries, including the to wives smoking 1-19 cigarettes
provide only indirect evidence on USA, smoking prevalence now varies and ≥20 cigarettes daily (Hirayama,
the lung cancer risk associated with markedly with indicators of income 1984). In 1981, increased lung cancer
involuntary exposure to tobacco and education, more recently tending risk in nonsmoking women married
smoke. Epidemiologists have directly to rise sharply with decreasing level to cigarette smokers was reported
tested the association between lung of education and income (U.S. (Trichopoulos et al., 1981). These
cancer and involuntary smoking Department of Health and Human investigators conducted a case-
utilising conventional designs: case- Services, 1989, 2004). In general, control study in Athens, Greece,
control and cohort studies. These exposure to SHS follows a similar which included cases with a final
studies not only provide evidence trend, and critics of the findings on diagnosis of lung cancer other than
relevant to causation, but also provide SHS and lung cancer have argued that adenocarcinoma or terminal bronchial
the characterisation of the risk that is uncontrolled confounding by lifestyle, carcinoma, and controls from the
needed to quantify the burden of lung occupation, or other factors may Hospital for Orthopedic Disorders.
cancer associated with SHS. explain the association. In fact, data The positive findings reported in 1981
for the USA do indicate a generally were unchanged with subsequent

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IARC Handbooks of Cancer Prevention

expansion of the study population analysis was carried out which RR was 2.01 (95% CI=1.33-2.60).
(Trichopoulos et al., 1983). included 37 published studies Another meta-analysis was carried
Subsequently, numerous case- (Hackshaw et al., 1997). An excess out to calculate a pooled estimate of
control and cohort studies have risk of lung cancer was estimated for RR of lung cancer associated with
addressed SHS and lung cancer. nonsmokers married to smokers as exposure to SHS in never smoking
Among the additional studies, a US 24% (95% CI=13-36%). Adjustment women exposed to smoking spouses
multicenter study merits specific for potential bias and confounding by (Taylor et al., 2007). Using 55 studies
discussion because of its size (651 diet did not alter the estimate. This (seven cohort, 25 population-based
cases and 1253 controls), and its meta-analysis was part of the basis case-control, and 23 non-population-
methodology, which addressed the for the conclusion by the UK Scientific based case-control studies) published
extant criticisms at the time of its Committee on Tobacco and Health through 2006, the authors found a
being conducted (Fontham et al., that SHS is a cause of lung cancer pooled RR for lung cancer associated
1994). The study found a significant (Scientific Committee on Tobacco with SHS from spouses of 1.27 (95%
increase in overall relative risk for and Health, 1998). A subsequent CI=1.17-1.37). For North America the
nonsmoking women married to IARC meta-analysis (IARC, 2004) RR was 1.15 (95% CI=1.03-1.28), for
smokers (odds ratio (OR)=1.26; 95% including 46 studies and 6257 cases, Asia, 1.31 (95% CI=1.16-1.48) and for
CI=1.04-1.54). Significant risk was yielded similar results: 24% (95% Europe, 1.31 (95% CI=1.24-1.52).
also associated with occupational CI=14-34%). Incorporating the results Since the two meta-analyses
exposure to SHS. from a cohort study with null results above and the 2006 Surgeon Gen-
Beginning with the 1986 NRC overall, but only 177 cases (Enstrom eral’s report on SHS, two new case-
report, there have been periodic & Kabat, 2003), did not change the control studies have been published
meta-analyses of the evidence on findings (Hackshaw, 2003). that confirm the association between
SHS and lung cancer. One of the first The most recent summaries SHS and lung cancer. A multicenter,
comprehensive meta-analyses was from the 2006 Surgeon General’s population-based case-control study
carried out by the US Environmental report are provided in Table 2.2. in Mexico City was conducted. For
Protection Agency for its 1992 risk The summary estimates continue to males and females combined, the
assessment (U.S. Environmental show an excess risk of around 20% OR for lung cancer associated with
Protection Agency, 1992). A meta- (e.g. pooled relative risk estimates SHS exposure at home was 1.8 (95%
analysis of the 31 studies published around 1.2) for nonsmokers married CI=1.3-2.6) after adjusting for age,
to that time was central in the to smokers. There is not strong sex, educational level, and access
Agency’s decision to classify SHS evidence for heterogeneity by gender to social security (Franco-Marina et
as a Group A carcinogen - namely or location. Workplace exposure is al., 2006). Among male and female
a known human carcinogen. The also associated with increased risk. never smokers, the crude OR for
meta-analysis considered the data The evidence is less convincing for lung cancer associated with SHS
from the epidemiologic studies by childhood exposure. exposure at home was 1.8 (95%
tiers of study quality and location Several other recent meta- CI=1.1-3.0) (Franco-Marina, 2008).
and used an adjustment method analyses further quantify the as- A study in never smoking Chinese
for misclassification of smokers as sociation between SHS and lung women aged 18-70 years, included
never smokers. Overall, the analysis cancer. A meta-analysis of 22 studies cases diagnosed with lung cancer
found a significantly increased risk of published through 2003 on workplace from hospitals in Beijing, Shanghai,
lung cancer in never smoking women SHS exposure and lung cancer was and Chengdu, and population controls
married to smoking men; for the performed (Stayner et al., 2007). matched for age and sex (Fang et
studies conducted in the USA, the The pooled relative risk (RR) was al., 2006). The OR for lung cancer
estimated relative risk was 1.19 (90% 1.24 (95% CI=1.18-1.29) associated associated with >50 person-years of
CI=1.04-1.35). with exposure to workplace SHS. exposure to SHS from home or work
In 1997, a comprehensive meta- Among highly exposed workers, the was 1.77 (95% CI=1.07-2.92).

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Health effects of exposure to secondhand smoke (SHS)

Table 2.2 Quantitative estimate of the risk of lung cancer with differing sources of exposure to secondhand smoke
(adapted from U.S. Department of Health and Human Services, 2006)

Study Data source Exposure vs. Referent RR 95% CI

Hackshaw et al., 1997 37 studies Smoking vs. nonsmoking spouse 1.24 1.13-1.36

IARC, 2004 38 studies Smoking vs. nonsmoking husband 1.23 1.13-1.34

Case-control
US Surgeon General, 2006 Smoking vs. nonsmoking spouse 1.21 1.13-1.30
(44 studies)

Spouse Cohort (8 studies) Smoking vs. nonsmoking spouse 1.29 1.12-1.49

54 studies Men Smoking vs. nonsmoking wife 1.37 1.05-1.79

Women Smoking vs. nonsmoking husband 1.22 1.13-1.31

USA and Canada Smoking vs. nonsmoking spouse 1.15 1.04-1.26

Europe Smoking vs. nonsmoking spouse 1.16 1.03-1.30

Asia Smoking vs. nonsmoking spouse 1.43 1.24-1.66

Nonsmokers
US Surgeon General, 2006 Workplace SHS vs. not 1.22 1.13-1.33
(25 studies)
Nonsmoking Men
Workplace Workplace SHS vs. not 1.12 0.86-1.50
(11 studies)
Nonsmoking Women
25 studies Workplace SHS vs. not 1.22 1.10-1.35
(25 studies)
Nonsmokers USA & Canada
Workplace SHS vs. not 1.24 1.03-1.49
(8 studies)
Nonsmokers Europe
Workplace SHS vs. not 1.13 0.96-1.34
(7 studies)
Nonsmokers Asia
Workplace SHS vs. not 1.32 1.13-1.55
(10 studies)

US Surgeon General, 2006 Men and Women Maternal smoking 1.15 0.86-1.52

Childhood Men and Women Paternal smoking 1.10 0.89-1.36

24 studies Men and Women Either parent smoking 1.11 0.94-1.31

Women Maternal smoking 1.28 0.93-1.78

Women Paternal smoking 1.17 0.91-1.50

USA (8 studies) Either parent smoking 0.93 0.81-1.07

Europe (6 studies) Either parent smoking 0.81 0.71-0.92

Asia (10 studies) Either parent smoking 1.59 1.18-2.15

17
IARC Handbooks of Cancer Prevention

Three prospective cohort studies et al., 2007). The age and ethnicity estimated that at least 3423, and
examining the relationship between standardised RR for mortality from perhaps as many as 8866, lung
SHS in nonsmokers have also been lung cancer associated with home cancer deaths were caused by SHS
published since the meta-analyses exposure to SHS was 1.00 (95% in the USA (California Environmental
by Taylor et al. (2007) and Stayner et CI=0.49-2.01) in the 1981-1984 Protection Agency: Air Resources
al. (2007). Most recently, in Japan, cohort and 1.16 (95% CI=0.70-1.92) Board, 2005). These calculations
a population-based cohort study of in the 1996-1999 cohort. illustrate that passive smoking must
28 414 lifelong nonsmoking women For this chapter, the prior meta- be considered an important cause of
aged 40-69 years was conducted, analyses were not updated with lung cancer death from a public health
collecting information on exposures these new estimates, as the existing perspective; exposure is involuntary
from spousal smoking, workplace estimates are based on an already and not subject to control.
exposure, and childhood exposure substantial body of research; they are
(Kurahashi et al., 2008). The hazard robust to additional data and IARC Bladder cancer
ratio (HR) for all lung cancer types has already concluded that passive
associated with living with a smoking smoking causes cancer. The US Surgeon General (U.S.
husband was 1.34 (95% CI=0.81- The extent of the lung cancer Department of Health and Human
2.21). The HR for adenocarcinoma burden associated with involuntary Services, 2006), California EPA
associated with living with a smoking smoking remains subject to some (California Environmental Protection
husband was significantly elevated at uncertainty, but estimates have been Agency: Air Resources Board,
2.03 (95% CI=1.07-3.86). For all lung made that are useful indications of 2005), and IARC (2004) reports did
cancer types, the HR associated the magnitude of the disease risk not address cancer of the bladder.
with SHS in the workplace was 1.32 (U.S. Department of Health and The literature search for this chapter
(95% CI=0.85-2.04), while the HR Human Services, 1986; Weiss, 1986; identified nine studies with informa-
specifically for adenocarcinoma California Environmental Protection tion on the association between
associated with SHS in the workplace Agency : Air Resources Board, 2005). exposure to SHS and bladder
was 1.93 (95% CI=0.88-4.23). In 1990, researchers reviewed the cancer (Tables 2.3a,b) with cases
A cohort study in 10 European risk assessments of lung cancer and identified between 1963 and 2004.
countries in the European Prospective passive smoking and estimated the A meta-analysis of these studies
Investigation into Cancer and Nutrition numbers of lung cancer cases in US was conducted to obtain a pooled
(EPIC) was conducted to examine the nonsmokers attributable to passive estimate of risk for bladder cancer
relationships of SHS and air pollution smoking (Repace & Lowrey, 1990). associated with exposure to SHS.
with lung cancer (Vineis et al., 2007). The range of the nine estimates, Since several studies presented
It was found that among never covering both never smokers and risk estimates stratified by mutually
smokers, the HR of lung cancer for former smokers, was from 58 to exclusive exposure categories (Burch
SHS exposure at home or work was 8124 lung cancer deaths for the et al., 1989; Zeegers et al., 2002;
1.05 (95% CI=0.60-1.82); at home: year 1988, with an overall mean of Chen et al., 2005; Samanic et al.,
0.84 (95% CI=0.38-1.9), at work: 1.28 4500 or 5000 excluding the lowest 2006), the Working Group pooled
(95% CI=0.67-2.4) (Vineis, 2008). estimate of 58. The 1992 estimate these estimates using random effects
Also examined was the of the California EPA, based on the meta-analysis. Risk estimates were
association between household epidemiologic data, was about 3000, then pooled across studies using
exposure to SHS and lung cancer including approximately 1500 and 500 random effects meta-analysis (Figure
mortality in two cohorts of New deaths in never smoking women and 2.1). The most comprehensive
Zealand lifelong nonsmokers aged men, respectively, and about 1000 exposure from each study was used
45-77 years, by linking census in long-term former smokers of both in calculating the combined risk
records, which included smoking sexes (U.S. Environmental Protection estimate of 0.97 (95% CI=0.74-1.28,
information, to mortality records (Hill Agency, 1992). The California EPA p for heterogeneity=0.153). Neither

18
Health effects of exposure to secondhand smoke (SHS)

cases and 202 controls matched


on age and sex were examined
(Phillips et al., 2005). Among never
smokers, exposure to SHS from
smoking by a spouse was associated
with a significantly increased risk of
intracranial meningioma (OR=2.0;
95% CI=1.1-3.5). Risk increased with
increasing years of exposure (p for
trend=0.02). Neither exposure to SHS
from another household member nor
exposure at work was associated
with risk, with ORs of 0.7 (95%
CI=0.4-1.1) and 0.7 (95% CI=0.4-1.2),
respectively (Tables 2.4a,b).

Breast cancer

In considering whether passive


smoking causes breast cancer, the
Figure 2.1 Pooled risk estimates from random effects meta-analysis of exposure to SHS
and bladder cancer evidence for active smoking needs
Alberg et al., 2007a and 2007b refer to estimates from the 1963 and 1975 cohorts respectively. All data included in the to be considered in assessing the
reference Alberg et al., 2007 plausibility of an association of breast
Sandler et al., 1985 refers to estimates cited in the reference Sandler et al., 1985a
cancer risk with SHS in nonsmokers.
There is some evidence to suggest
the Begg’s nor Egger’s tests indicated a husband’s consumption of 1-14 that an association between tobac-
publication bias with p-values of 0.602 cigarettes/day the RR was 3.03 (90% co smoke and breast cancer is
and 0.654, respectively. CI=1.07-8.58), for 15-19 cigarettes/ biologically plausible. Studies have
day the RR was 6.25 (90% CI=2.01- shown that carcinogens in tobacco
Brain cancer 19.43), and the RR was 4.23 (90% smoke reach breast tissue (Petrakis
CI=1.53-12.19) for 20+ cigarettes/ et al., 1978, 1988 ; Li et al., 1996)
The California EPA report on SHS day. However, there were only 34 and are mammary mutagens (Nagao
in 2005 reviewed the previous cases of death from brain cancer. et al., 1994; Dunnick et al., 1995; el-
literature regarding the association The 2005 California EPA report Bayoumy et al., 1995). However, other
between SHS exposure and brain concluded that the epidemiological studies using biomarkers have found
cancer in adults; four studies were evidence for an association between an association between smoking
considered. In the first published SHS and risk of brain tumors was and decreased levels of estrogen
study, brain tumor mortality in a large weak and inadequately researched, (MacMahon et al., 1982 ; Michnovicz
scale cohort of nonsmoking married the same conclusion reached earlier et al., 1986), which implies that active
women in Japan was examined in the 1997 California EPA report smoking might decrease the risk of
(Hirayama, 1984). It was reported on SHS. Since the 2005 California breast cancer.
that the rate ratio (RR) of death from EPA report, only one new report was
brain cancer was increased among identified. Associations between SHS
women with smoking husbands exposure and the risk of intracranial
when compared to women who meningioma in a population-based
were married to nonsmokers. For case-control study that included 95

19
20
Table 2.3a Exposure to SHS and bladder cancer - Cohort studies

Adjustment
Reference, Relative risk
Cohort description Exposure assessment Exposure categories for potential Comments
location, period (95% CI)
confounders
Zeegers et al,. 2002 3346 adults 55-69 Self-administered Never-smoking partner 1 Age and gender Results
years at enrollment (619 questionnaire (adulthood) for never
The Netherlands microscopically confirmed smokers
1986-1992 incident carcinomas of the Ex-smoking partner (adulthood) 0.95 (0.46-2.0)
urinary bladder, ureters, or
urethra); 6.3 years of follow- Current-smoking partner 0.74 (0.29-1.9)
up with no subjects lost (adulthood)

Parents did not smoke 1


IARC Handbooks of Cancer Prevention

(childhood)

Parents smoked (childhood) 1.2 (0.56-2.4)

Low exposure to SHS at work 1


(adulthood)

High exposure to SHS at work 1.4 (0.70-2.6)


(adulthood)

No exposure to SHS at home 1


or at work (adulthood)

1 to <3 hours per day of 0.69 (0.33-1.4)


exposure to SHS at home or
work (adulthood exposure)

3+ hours per day of exposure 0.64 (0.29-1.4)


to SHS at home or work
(adulthood exposure)

Bjerregaard et al., 2006 126 908 adults 25-70 years Self- and interviewer- No SHS exposure (at baseline) 1 Results
at enrollment (115 cases of administered at home and/or work for never
Denmark, France, primary bladder cancer in questionnaire smokers
Sweden never smokers); average SHS exposure (at baseline) at 0.82
1991-2004 follow-up time was 6.3 years home and/or work (adulthood (0.46-1.48)
exposure)

No SHS exposure during 1 Fruit and


childhood vegetable intake,
SHS exposure in
SHS exposure during 2.02 childhood
childhood (from parents or (0.94-4.35)
others)
Adjustment
Reference, Relative risk
Cohort description Exposure assessment Exposure categories for potential Comments
location, period (95% CI)
confounders
Alberg et al., 2007 24 823 never smoking Self-administered Never smokers with noncurrent 1 Age, education, Results
women, aged ≥ 25 years questionnaire SHS exposure in the home marital status for never
Maryland, USA at enrollment with no prior smokers
1963-1978 cancer (23 cases of invasive Current SHS exposure in the 2.3 (1.0-5.4)
cohort bladder cancer) home (any source)

Former SHS exposure in the 0.3 (0.1-2.5)


home (any source)

Current SHS exposure in the 1.8 (0.8-4.5)


home (any source)

Exposed to SHS in the home 1.1 (0.3-3.8)


from spouse only

Exposed to SHS in the home 3.0 (1.2-7.9)


from other (than spouse)
household members only

Alberg et al., 2007 26 381 women, aged ≥ 25 Self-administered Never smokers with noncurrent 1 Age, education, Results
years at enrollment with no questionnaire SHS exposure in the home marital status for never
Maryland, USA prior cancer (30 cases of smokers
1975-1994 invasive bladder cancer) Current SHS exposure in the 0.9 (0.4-2.3)
cohort home (any source)

Former SHS exposure in the 0.8 (0.3-2.0)


home (any source)

Current SHS exposure in the 0.9 (0.3-2.2)


home (any source)

Exposed to SHS in the home 1.2 (0.4-3.6)


from spouse only

Exposed to SHS in the home 0.4 (0.1-3.3)


from other (than spouse)
household members only
Health effects of exposure to secondhand smoke (SHS)

21
22
Table 2.3b Exposure to SHS and bladder cancer - Case-control studies

Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)
confounders
Sandler et al., 1985a 6 patients 15-59 years 489 friend and Self- Nonsmoking spouse or 1 Only married
with cancer of the community controls administered never married individuals
North Carolina, USA urinary tract; individually matched questionnaire were eligible
1979-1981 40% response rate on gender, age, and Spouse smoked regularly 1.1 (0.2-7.6) Age and to be
race; 75% response (at least 1 cig/day for at education considered
rate least 6 months) any time “exposed”
during marriage

Sandler et al, 1985b 5 patients 15-59 years 438 friend and Self- Not exposed to SHS from 1 None of
IARC Handbooks of Cancer Prevention

with cancer of the community controls administered father during first 10 yrs the bladder
North Carolina, USA urinary tract; individually matched questionnaire of life cancer
1979-1981 70% response rate on gender, age, cases were
and race; control SHS exposure from father 0.8 (0.1-5.7) exposed to
response rate not during first 10 yrs of life SHS from the
stated mother

Burch et al., 1989 826 adults 35-79 826 population Interviewer- Among nonsmokers:
years with primary controls individually administered
Alberta and Ontario, bladder cancer without matched for age, questionnaire No SHS exposure at home 1
Canada recurrent malignant gender, and area
1979-1982 neoplasms of the of residence; 53% Males:
bladder or invasion response rate exposure at home 0.94 (0.45-1.95)
of the bladder from
primary prostatic Females:
cancer; exposure at home 0.75 (0.33-1.71)
67% response rate
No SHS exposure at work 1

Males:
exposure at home 0.97 (0.50-1.91)

Females:
exposure at home 0.93 (0.48-1.79)

Chen et al., 2005 14 adults ≥50 years 202 hospital controls Interviewer- Men: Age, BMI, Interaction
with newly diagnosed (fracture and administered No SHS exposure 1 cumulative present
Taiwan bladder cancer cataract patients) questionnaire arsenic, hair dye for arsenic
1996-1999 ≥50 years SHS exposure 7.16 (1.87-27.4) usage, education measured by
secondary
Women: methylation
No SHS exposure 1 index
Results
SHS exposure 1.09 (0.42-2.80) among
nonsmokers
presented
Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)
confounders
Samanic et al., 2006 1219 White adults 1271 hospital Interviewer- Men: Age, hospital Sum of the
aged 21-80 years controls (with administered No childhood SHS 1 region, fruit years spent
Spain with incident bladder conditions questionnaire or vegetable at each
1998-2000 cancer without considered unrelated consumption, childhood
previous cancer of the to smoking), <18 yrs SHS exposure 1.2 (0.6-2.3) and high-risk residence up
lower urinary tract, or individually matched occupation to age 18
patients with bladder on age, gender, 18 yrs SHS exposure 0.9 (0.3-2.6)
tumors secondary to race, and hospital; p for trend= 0.92
other malignancies; 88% response rate No residential adulthood 1
84% response rate SHS Sum of the
years spent
>0 to 26 person-yrs of 1.1 (0.5-2.4) at each adult
adulthood residential SHS residence
times N of
>26 to 54 person-yrs of 0.8 (0.3-2.2) smokers per
adulthood residential SHS / res.

>54 person-yrs of 1.3 (0.5-3.2)


residential adulthood SHS

p for trend 0.74

No occupational adulthood 1
SHS Sum of the
years spent
>0 to 135 person-yrs of 0.6 (0.2-1.6) at each job
occupational adulthood times N of
SHS smokers per
job
>135 to 240 person-yrs of 0.2 (0.1-0.7)
occupational adulthood
SHS

>240 person-yrs of 0.6 (0.2-1.4)


occpationaladulthood SHS

p for trend 0.58

Women:
No childhood SHS 1

<18 yrs childhood SHS 0.7 (0.3-1.4)

18 yrs childhood SHS 0.6 (0.2-1.7)

p for trend 0.24

No residential adulthood 1
SHS

>0 to 26 person-yrs of 2.2 (0.8-6.2)


Health effects of exposure to secondhand smoke (SHS)

23
residential adulthood SHS
24
Table 2.3b Exposure to SHS and bladder cancer - Case-control studies

Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)
confounders
Samanic et al., 2006 >26 to 54 person-yrs of 1.9 (0.7-4.8)
residential adulthood SHS
Spain
1998-2000 >54 person-yrs of 0.8 (0.3-1.9)
residential adulthood SHS

p for trend 0.27

No occupational adulthood 1
IARC Handbooks of Cancer Prevention

SHS

>0 to 135 occupational 1.7 (0.7-4.0)


person-yrs of adulthood
SHS

>135 to 240 person-yrs of 1.7 (0.6-4.4)


occupational adulthood
SHS

>240 person-yrs of 3.3 (1.1-9.5)


occupational adulthood
SHS

p for trend 0.03

Jiang et al., 2007 148 never smoking 292 never smoking Interviewer- No SHS exposure during 1 Age, gender, Confidence
Asian adults aged population controls, administered childhood race, education, intervals not
California, USA 25-64 years, with matched for age, questionnaire adulthood SHS provided
1987-1999 histologically- gender, race, and SHS exposure during 0.91
confirmed bladder area of residence; childhood
cancer; 96.4% response rate
89.7% response rate SHS exposure during 0.88
childhood (1 smoker)

SHS exposure during 0.97


childhood (>1 smoker)

No SHS exposure during 1 Age, gender,


adulthood in a domestic education,
setting childhood SHS,
adulthood SHS
SHS exposure during 0.85 (occupational
adulthood (domestic and social
setting) settings)

SHS exposure during 0.88


adulthood (domestic
setting, <10 yrs)
Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)
confounders
Jiang et al., 2007 SHS exposure during 0.82
adulthood (domestic
California, USA setting, ≥10 yrs)
1987-1999
No SHS exposure 1 Age, gender,
during adulthood in an education,
occupational setting childhood SHS,
adulthood SHS
SHS exposure during 0.98 (domestic and
adulthood (occupational social settings)
setting)

SHS exposure during 0.93


adulthood (occupational
setting, <10 yrs)

SHS exposure during 0.98


adulthood (occupational
setting, ≥10 yrs)

No SHS exposure during 1 Age, gender,


adulthood in a social education,
setting childhood SHS,
adulthood SHS
SHS exposure during 1.06 (domestic and
adulthood (social setting) occupational
settings)
SHS exposure during 1.29
adulthood (social setting,
<10 yrs)

SHS exposure during 0.92


adulthood (social setting,
≥10 yrs)

Low (0) cumulative index 1 Age, gender,


of SHS exposure education

Intermediate (1-3) 1.61


cumulative index of SHS
exposure

High (4-8) cumulative 1.28


index of SHS exposure
Health effects of exposure to secondhand smoke (SHS)

25
26
Table 2.4a Exposure to SHS and brain cancer - Cohort studies

Reference, Relative risk Adjustment for


Cohort description Exposure assessment Exposure categories Comments
location, period (90% CI) potential confounders

Hirayama, 1984 91 540 nonsmoking, Interviewer-administered Nonsmoking husband 1 Husband’s age Same data used
married women questionnaire in Hirayama,
Japan ≥40 years (34 deaths Husband smokes 1985
1966-1981 due to brain tumors) 1-14 cig/day 3.03 (1.07-8.58)

Husband smokes
15-19 cig/day 6.25 (2.01-19.43)

Husband smokes
≥20 cig/day 4.32 (1.53-12.19)
IARC Handbooks of Cancer Prevention

Hirayama, 1985 91 540 nonsmoking, Interviewer-administered Nonsmoking husband 1 Husband’s age Same data used
married women questionnaire in Hirayama,
Japan ≥40 years (34 deaths Husband is ex-smoker or 1984
1966-1981 due to brain tumors) smokes 1-19 cig/day 3.28 (1.21-8.92)

Husband smokes
≥20 cig/day 4.92 (1.72-14.11)

Table 2.4b Exposure to SHS and brain cancer in adults - Case-control studies

Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)
confounders
Sandler et al., 1985a 38 patients 15-59 489 friend and Self- Non exposed to SHS 1 Age, sex, Smoking
years with eye, brain, community controls; administered active smoking wives included
North Carolina, USA and other nervous 75% response rate questionnaire Spouse smoked regularly 0.7 (0.3-1.5)
1979-1981 system cancers; (at least 1 cig/day for at
66% response rate least 6 months) any time
during marriage

Ryan et al., 1992 170 adults 25-74 years 417 community Interviewer- RR (95% CI) Age, sex, Active
with newly diagnosed controls, frequency administered for glioma active smoking smokers
Australia cancer of the brain matched on age, questionnaire included
1987-1990 and meninges (110 gender, and postal Non exposed to SHS 1
glioma cases and 60 code; 63.3%
meningioma cases); response rate Ever exposed to SHS 1.24 (0.76-2.00)
90.5% response rate
1-12 yrs SHS exposure 1.33 (0.69-2.56)

13-27 yrs SHS exposure 1.17 (0.60-2.27)

28+ yrs SHS exposure 1.21 (0.62-2.37)

Nonsmokers, ever exposed 1.30 (0.62-2.7)


to SHS
Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)
confounders

Ryan et al., 1992 RR (95% CI) for


meningioma
Australia
1987-1990 Non exposed to SHS 1

Ever exposed to SHS 1.91 (1.01-3.63)

1-12 yrs SHS exposure 1.55 (0.66-3.65)

13-27 yrs SHS exposure 2.15 (0.91-6.38)

28+ yrs SHS exposure 2.12 (0.98-4.71)

Nonsmokers, ever exposed 2.45 (0.98-6.14)


to SHS

Hurley et al., 1996 416 histologically 422 population Questionnaires Spouse does not smoke 1 Results
confirmed gliomas controls matched by and interviews among
Australia age and sex Living with smoker 0.97 (0.61-1.53) nonsmokers
1987-1991

Phillips et al., 2005 95 adult patients 202 community Spouse does not smoke 1 Conditional
never smokers/haven’t controls, individually regression
Washington, USA smoked in last 10 matched on age Spouse smokes 2.0 (1.1-3.5) matched on
1995-1998 years with intracranial and sex; 55% age and sex
meningioma; response rate from Spouse smoked 1.4 (0.7-3.1) and adjustment
84% overall response random digit dialing <13 yrs for education
rate and 67% response
rate from Medicare Spouse smoked 2.3 (0.9-5.9)
eligibility lists 13-28 yrs

Spouse smoked 2.7 (1.0-7.1)


>28 yrs

p for trend 0.02

No SHS exposure at home 1


from other household
members

SHS exposure at home 0.7 (0.4-1.1)


from other household
members (not spouse)

No SHS exposure at work 1

SHS exposure at work 0.7 (0.4-1.2)


Health effects of exposure to secondhand smoke (SHS)

27
IARC Handbooks of Cancer Prevention

The 2001 and 2004 reports of the US is a cause of breast cancer, although effects, cohort studies overall did
Surgeon General reviewed further it did not carry out a full, systematic not find a causal association (IARC,
evidence related to smoking and review (California Environmental 2004). Additionally, the lack of a
estrogen, finding that smoking was Protection Agency: Air Resources positive dose-response relationship
associated with a decreased risk of Board, 2005). Two cohort studies and association with active smoking
endometrial cancer and an earlier published in 2004 found a significant weigh against the possibility of an
age at menopause (U.S. Department increase in risk of breast cancer (Al- increased risk of breast cancer
of Health and Human Services, Delaimy et al., 2004; Reynolds et al., from SHS exposure. Subsequently,
2001, 2004). These anti-estrogenic 2004). However, the US Surgeon the US Surgeon General came to
consequences of active smoking General concluded that sufficient similar conclusions (U.S. Department
have been construed as implying evidence has not accumulated of Health and Human Services, 2006).
that breast cancer risk would be to suggest a causal association Using data from seven prospective
reduced for active smokers in between active smoking and breast cohort studies and 14 case-control
comparison with never smokers. The cancer (U.S. Department of Health studies, a meta-analysis was per-
evidence is not consistent, however, and Human Services, 2006). formed. Sensitivity analyses
and uncertainty remains about the More than 20 epidemiologic showed that cohort studies overall
effect of smoking on blood estrogen studies have been published found null results and studies that
levels. These possibly opposing specifically addressing the as- adjusted for potential confounding
biological consequences of active sociation between SHS and breast showed weaker associations (U.S.
smoking may explain why review of cancer. Several major reports, Department of Health and Human
the epidemiologic data has found an including the IARC Monograph 83, Services, 2006). Furthermore, the
overall null effect of active smoking the 2005 California EPA report, and possibility of publication bias was
on the risk of breast cancer. the 2006 US Surgeon General’s evaluated, and found that less precise
Since the 1960s, there have been report, have reviewed the evidence for studies tended to have more positive
more than 50 studies investigating the an association between SHS exposure results. Finally, after reviewing all of
association between active smoking and breast cancer (IARC, 2004 ; the evidence using the criteria for
and breast cancer. In 2002, a pooled California Environmental Protection causality, the US Surgeon General’s
analysis of data from 53 studies Agency: Air Resources Board, 2005 ; report found that overall the evidence
was conducted and found a relative U.S. Department of Health and Human is inconsistent and concluded that the
risk of 0.99 (95% CI=0.92-1.05) for Services, 2006). The California EPA data is suggestive, but not sufficient
women who were current smokers conducted a meta-analysis using six to infer a causal association between
compared with women who were cohort studies and 12 case-control SHS exposure and breast cancer.
lifetime nonsmokers (Hamajima et studies that were deemed to provide Since the 2006 US Surgeon
al., 2002). One possible explanation the “best evidence.” They found an General’s report, three new case-
for the null results is that the anti- increased risk of 25% (95% CI=8- control studies examining the
estrogenic effects of smoking may 44%) overall, and concluded that there association between SHS and breast
offset the potentially carcinogenic is sufficient evidence for a causal cancer have been identified. A large
effects on the risk of breast cancer. association among premenopausal population-based case-control study
Subsequently, the 2004 reports of women (California Environmental in Poland (2386 cases and 2502
the US Surgeon General and IARC Protection Agency: Air Resources controls) examining the associations
concluded that the weight of evidence Board, 2005). Among post- between active and passive smoking
strongly suggests that there is no menopausal women, there was no and risk of breast cancer was
causal association between active indication of an association. In 2004, conducted (Lissowska et al., 2006).
smoking and breast cancer (IARC, IARC concluded that the evidence Never smoking women ever exposed
2004). One year later, the California is inconsistent, and although some to SHS at home or at work did not have
EPA concluded that active smoking case-control studies found positive a significantly elevated risk of breast

28
Health effects of exposure to secondhand smoke (SHS)

exposure categories, these estimates


were pooled using random effects
meta-analysis. Risk estimates were
then also pooled across studies using
random effects meta-analysis (Table
2.5; Figures 2.2a-c). Pooled estimates
were calculated for three population
samples: all women in a study
(regardless of menopausal status),
premenopausal women, and post-
menopausal women. Three exposure
categories were considered: spouse/
partner in adulthood, adulthood work
exposure, and childhood parental
exposure in the home.
For all women, the updated,
combined relative risk from ex-
posure from a spouse or partner
was 1.14 (95% CI=0.97-1.34, p
Figure 2.2a Pooled risk estimates from random effects meta-analysis of for heterogeneity=0.002), slightly
exposure to SHS from spouse and breast cancer in all women
smaller than the US Surgeon Gen-
eral’s report’s combined estimate
cancer (OR=1.10; 95% CI=0.84-1.45). Southwestern USA (1527 NHW and of 1.18 (95% CI=0.99-1.39, p for
In addition, a trend was not observed 798 HAI cases; 1601 NHW and 924 heterogeneity=0.002). The updated,
between increasing hours/day-years HAI controls) (Slattery et al., 2008). combined estimate used the pooled
of SHS and risk of breast cancer (p for Among never smokers, exposure (random effects) results for duration
trend=0.24) (Lissowska et al., 2007). to SHS only increased the odds of of exposure to SHS from a partner in
A population-based case-control premenopausal breast cancer in HAI never smoking women aged 36-45
study of breast cancer in women women (OR=2.3; 95% CI=1.2-4.5). In years (RR=0.91; 95% CI=0.67-1.22)
aged 36-45 years (639 cases and addition, HAI premenopausal never (Roddam et al., 2007). The combined
640 controls) was conducted. Among smoking women with the rs2069832 RR for all women from occupational
never smoking women, there was no IL6 GG genotype exposed to ≥10 SHS exposure was 1.10 (95% CI=0.88-
significant association between SHS hours of SHS per week, compared 1.38, p for heterogeneity=0.004),
exposure from a partner in the home to those with no SHS exposure, had slightly larger than the US Surgeon
and risk of breast cancer (RR=0.89; over four times the odds of breast General’s report’s combined estimate
95% CI=0.64-1.25). Additionally, cancer (OR=4.4; 95% CI=1.5-12.8, p of 1.06 (95% CI=0.84-1.35, p for
there was not a trend with increasing for interaction=0.01). heterogeneity=0.008). No new data
duration of SHS exposure (p=0.31) The meta-analysis of SHS were available for updating estimates
and heterogeneity of the association exposure and breast cancer risk in the for childhood parental SHS exposures
comparing pre- and postmenopausal 2006 US Surgeon General’s report on since the 2006 US Surgeon General’s
women (p=0.35) (Roddam et al., involuntary smoking, was updated for report. The Begg’s and Egger’s tests
2007). The association between this Handbook to include the three provided evidence for publication
SHS and risk of breast cancer was new case-control studies identified by bias in studies among all women for
evaluated in non-Hispanic white literature search. Since many of the occupational SHS exposure during
(NHW) and Hispanic/American studies provided risk estimates that adulthood.
Indian (HAI) women from the were stratified by mutually exclusive

29
IARC Handbooks of Cancer Prevention

Updated combined estimates


from this meta-analysis were
also calculated for studies
stratified by menopausal status.
For premenopausal women, the
updated combined relative risk
from exposure from a spouse or
partner was 1.16 (95% CI=0.91-
1.48, p for heterogeneity=0.074),
slightly smaller than the US Surgeon
General’s report’s combined est-
imate of 1.25 (95% CI=0.97-1.62, p
for heterogeneity=0.164). Among
postmenopausal women, the
updated combined relative risk
from exposure from a spouse or
partner was 1.02 ((95% CI=0.76-
1.36), p for heterogeneity=0.143),
Figure 2.2b Pooled risk estimates from random effects meta-analysis of almost the same as the US Surgeon
exposure to SHS from spouse and breast cancer in premenopausal women General’s report’s combined est-
imate of 1.00 (95% CI=0.73-1.38,
p for heterogeneity=0.080). These
updated combined estimates include
results from Roddam et al. (2007). No
new data were available, since the
2006 US Surgeon General’s report,
for updating combined estimates for
pre- and postmenopausal women’s
workplace or childhood SHS ex-
posures. The Begg’s and Egger’s
tests did not provide evidence of
publication bias for studies among
premenopausal women for SHS
exposure from spouse or partner.
The results for the relationship
between SHS exposure and
breast cancer risk from this meta-
analysis diverge from those of the
2005 California EPA report on
environmental tobacco smoke. In
addition to inclusion of the recently
published studies contained in this
Handbook, the selection of studies
included in the California EPA meta-
Figure 2.2c Pooled risk estimates from random effects meta-analysis of analyses is a likely explanation for
exposure to SHS from spouse and breast cancer in postmenopausal women this difference.

30
Health effects of exposure to secondhand smoke (SHS)

Using six case-control studies judged

(0.53-1.29)

(0.86-1.26)
(0.76-1.36)
Updated

[0.086]

[0.242]
[0.143]
unlikely to have missed three major

0.83

1.04
1.02
Table 2.5 Random effects meta-analysis results of SHS and breast cancer (2006 US Surgeon General’s report and updated estimates by

sources of lifetime SHS exposure


Postmenopausal
(childhood home, adulthood home,
and work), the California EPA report
n

3
presented a combined relative
risk estimate among all women

(0.53-1.29)

(0.86-1.26)
(0.73-1.38)
SG (2006)

of 1.89 (95% CI=1.52-2.36, p for

[0.086]
[0.080]

[0.242]
0.83
1.00

1.04
heterogeneity=0.265). The analysis,
which included all 17 studies, yielded
a combined relative risk among all
women of 1.40 (95% CI=1.17-1.68,
n

3
p for heterogeneity=0.0). Among
studies which presented results
(0.70-2.09)

(0.90-1.45)
(0.91-1.48)
Updated

[0.000]

[0.339]
for premenopausal women, the
[0.074]

1.21
1.16

1.14
California EPA report presented a
combined relative risk estimate from
six case-control studies deemed
Premenopausal

unlikely to have missed major


n

sources of lifetime SHS exposure


to be 2.20 (95% CI=1.70-2.85, p for
(0.70-2.09)

(0.90-1.45)
(0.97-1.62)
SG (2006)

heterogeneity=0.361), while using


[0.000]

[0.339]
[0.164]
1.25

1.21

1.14

all 11 case-control studies yielded a


combined relative risk of 1.99 (95%
CI=1.49-2.66).
n

Cervical cancer
(0.88-1.38)
(0.97-1.34)

(0.90-1.12)
Updated

The US Surgeon General (U.S.


[0.002]

[0.004]

[0.101]

[in brackets]: p-value for test of heterogeneity (null hypothesis is no heterogeneity)


1.01
1.10
1.14

Department of Health and Human


Services, 2006), the California EPA
(California Environmental Protection
Agency: Air Resources Board, 2005),
All women

11
n

and the IARC (2004) reports all


addressed the relationship between
(0.84-1.35)
(0.99-1.39)

(0.90-1.12)
SG (2006)

SHS exposure and risk of cervical


[0.008]
[0.002]

[0.101]
1.06

1.01
1.18

cancer. A literature search identified


n: number of studies included in each analysis
Volume 13 Working Group)

a total of 12 studies with 13 study


samples (Tables 2.6a,b) that examined
the association between exposure to
10
n

SHS and cervical cancer.


SG: US Surgeon General
Exposure

*No new studies


(parental)*
(spousal)

(work)
Adult

Adult

Child

31
32
Table 2.6a Exposure to SHS and cervical cancer - Cohort studies

Adjustment
Reference, location, Exposure Relative risk
Cohort description Exposure categories for potential Comments
period assessment (95% CI)
confounders
Hirayama, 1981 91 540 nonsmoking Interviewed about risk RR (90% CI)
wives followed for 14 factors
Tokyo, Japan, years Husband nonsmoker 1
1966-1979
Husband ex-smoker or
1-19 cig/day 1.15

Husband smokes
20+ cig/day 1.14
IARC Handbooks of Cancer Prevention

p for trend 0.249

Hirayama, 1984 91 540 nonsmoking Interviewed about risk RR (90% CI) Age by Mantel-
wives followed for 16 factors Haenszel method
Tokyo, Japan years Husband nonsmoker 1
1966-1981
Husband smokes
1-14 cig/day 1.67 (0.67-4.20)

Husband smokes
15-19 cig/day 2.02 (0.64-6.33)

Husband smokes
20+ cig/day 2.55 (1.04-6.27)

p for trend 0.0248

Jee et al., 1999 Korean women aged Questionnaires from Husband’s smoking status Age of wives
40-88 who received 1992, 1993, and 1994 and husbands,
Korea health insurance from conducted in 416 Husband never smoker 1.0 SES, residency,
1994-1997 KMIC hospitals husband’s vegetable
Husband ever smoked 0.9 (0.6-1.3) consumption,
husband’s occupation
Husband current smoker 0.9 (0.6-1.2)

Nishino et al., 2001 9675 Japanese lifelong Self-administered Husband nonsmoker 1.0
nonsmoking women questionnaire
Japan completed in 1984 Husband smokes 1.1 (0.26-4.5)
1984-1993
p value 0.925
Adjustment
Reference, location, Exposure Relative risk
Cohort description Exposure categories for potential Comments
period assessment (95% CI)
confounders
Tay & Tay, 2004 623 women attending OR (95% CI) Age, parity, age at Not restricted to
colposcopy clinic for first intercourse, birth never smokers
Singapore evaluation between Husband nonsmoker 1 control pill use, patients
1995-2001 1995 and 2001 smoking
LSIL: 1.03 (0.990-1.071) LSIL: Low grade
Husband smokes 1 more squamous intra-
cig/day epithelial lesion

HSIL: 1.046 (1.013-1.080) HSIL: High


Husband smokes 1 more grade
cig/day squamous
intraepithelial
lesion

Trimble et al., 2005 Female residents of Mailed questionnaires No Passive Smoking (PS) 1.0 Age Analysis among
Washington County, and door-to-door Never smokers.
Washington County, MD who agreed to interviews PS only 2.5 (1.3-3.3) PS refers
MD, 1963-1978 participate in original to passive
cohorts Other household member 2.6 (1.6-4.0) smoking

Spouse 2.2 (1.2-4.3)

Never smoker, no PS 1.0 Age, education, marital


status, religious
PS only 2.1 (1.3-3.3) attendance

Other household member 2.3 (1.1-4.9)

Spouse 2.0 (1.2-3.3)

Washington County, No PS 1.0 Age


MD, 1975-1994
PS only 1.3 (0.7-2.3)

Other household member 1.3 (0.7-2.5)

Spouse 1.6 (0.7-3.9)

Never smoker, no PS 1.0 Age, education, marital


status, religious
PS only 1.4 (0.8-2.4) attendance

Other HH member 1.3 (0.6-3.2)

Spouse 1.6 (0.7-3.9)


Health effects of exposure to secondhand smoke (SHS)

33
34
Table 2.6b Exposure to SHS and cervical cancer - Case-control studies

Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)*
confounders
Buckley et al., 1981 31 husbands of 62 husbands of Husbands and Cervical dysplasia, RR Matched for age
married women with patients without wives interviewed carcinoma in situ: and age at first
England cervical dysplasia, cervical dysplasia, either at health husband’s smoking intercourse
1974-1979 carcinoma in situ, carcinoma in situ, clinic or at home status
or invasive cervical or invasive cervical
cancer cancer matched for Nonsmoker 1
age and age at first
intercourse Ex-smoker 4.42
IARC Handbooks of Cancer Prevention

Current smoker 1.91

Chi-square for trend 2.42

Invasive carcinoma: RR Matched for age


husband’s smoking and age at first
status intercourse

Nonsmoker 1

Ex-smoker 1.82

Current smoker 4.44

Chi-square for trend 2.17

Invasive cervical RR Matched for age


cancer: husband’s and age at first
smoking status intercourse

Nonsmoker 1

Ex-smoker 2.69

Current smoker 3.21

Chi-square for trend 4.59

Brown et al., 1982 33 patients with 29 with Interview using Invasive cancer: Matched for age Unmatched
invasive or in situ hysterectomies for questionnaire Husband nonsmoker 1 at surgery, parity, crude ORs
Canada cervical cancer non-cancer reasons social class, and calculated from
1959-1968 Husband smokes date of surgery table
<20 cig/day 0.55

Husband smokes
20-40 cig/day 1.25

Husband smokes
>40 cig/day 6.00
Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)*
confounders

Brown et al., 1982 Total cervical


cancer:
Canada Husband nonsmoker 1
1959-1968
Husband smokes
<20 cig/day 1.36

Husband smokes
20-40 cig/day 5.00

Husband smokes
>40 cig/day 15.00

Sandler et al., All cancer cases Friends or Mailed Mother nonsmoker 1 None Results
1985b (except basal cell acquaintances questionnaire and presented
skin) from North of case without telephone call Mother smoked 0.77 among
University of North Carolina Memorial cancer, of similar nonsmokers;
Carolina Hospital tumor age (±5 yrs), sex, Father nonsmoker 1 CIs not
1979-1981 registry diagnosed and race, or through presented
between 1979 and telephone sampling Father smoked 1.7
1981 and alive in
1981; aged 15-59

Sandler et al., All cancer cases Friends or Mailed Spouse did not smoke 1 Results among
1985a (except basal cell acquaintances questionnaire and nonsmokers
skin) from North of case without telephone call Spouse smoked 2.1 (1.2-3.9) presented
University of North Carolina Memorial cancer, of similar
Carolina Hospital tumor age (+/- 5 yrs), sex,
1979-1981 registry diagnosed and race, or through
between 1979 and telephone sampling
1981 and alive in
1981; aged 15-59

Hellberg et al., 140 pregnant 280 pregnant age- Midwife Male partner 1 Unmatched OR
1986 women matched women administered nonsmoker calculated from
histologically (2 for each case) questionnaire and table
Falu Hospital, diagnosed also visiting the mailed it Male partner smokes 2.01 (1.84-2.21)
Sweden with cervical maternity clinic on
1977-1981 intraepithelial the same occasion p value <0.001
neoplasia using with normal smears
colposcopy
Slattery et al., 1989 266 histologically 408 age- and Personal No hrs/day of passive 1 Age, education, Results among
confirmed incident residence-matched interviews in smoking (PS) church attendance, never smokers
Utah cases of carcinoma controls using respondents’ # sexual partners presented (81
1984-1987 in situ or invasive random digit homes 0.1-0.9 hrs/day 1.14 (0.45-2.94) of woman; age and cases and 305
carcinoma identified dialing sampling residence matched controls).
through rapid without history of 1.0-2.9 hrs/day 1.57 (0.52-4.73) PS refers to
reporting system hysterectomy before passive smoking
1984 or missing data ≥3.0 hrs/day of 3.43 (1.23-9.54)
Health effects of exposure to secondhand smoke (SHS)

35
36
Table 2.6b Exposure to SHS and cervical cancer - Case-control studies

Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)*
confounders
Slattery et al., No hrs/day of PS 1
1989 in-home

Utah 0.1-1.5 hrs/day 0.62 (0.25-1.53)


1984-1987
>1.5 hrs/day 2.66 (1.15-6.13)

No hrs/day of PS 1
away from home
IARC Handbooks of Cancer Prevention

0.1-1.5 hrs/day 1.33 (0.58-3.07)

>1.5 hrs/day 2.3 (0.89-5.95)

None in-home PS 1

Little in-home PS 1.86 (0.37-9.37)

Some in-home PS 1.49 (0.44-5.09)

A lot in-home PS 2.93 (1.08-7.94)

None away from 1


home PS

Little away from home 1.58 (0.68-3.66)


PS

Some away from 1.11 (0.49-2.50)


home PS

A lot away from home 1.59 (0.57-4.45)


PS
Coker et al., 1992 103 cases with CIN 268 normal controls; Interviewed by No PS at home 1 Age, race, Results for
grades II and III; aged 18-45 years; telephone or in education, # sex nonsmoking
University of North aged 18-45 years; black or white and person <17 yrs at home 1.5 (0.5-4.9) partners, # Paps in women
Carolina Black or White non-pregnant; last 5 yrs, genital
1987-1988 and non-pregnant; response rate 18+ yrs at home 0.4 (0.1-1.3) warts
response rate 92% 91.8%
No PS at work 1

1-4 yrs at work 1.7 (0.5-5.1)

5+ yrs at work 0.4 (0.1-2.5)

Not exposed 1

Parent only 0.4 (0.1-1.2)


Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)*
confounders

Coker et al., 1992 Husband only 1.5 (0.3-6.2)

University of North Parent and husband 0.4 (0.1-1.9)


Carolina
1987-1988 Others only 1.8 (0.4-8.4)

Hirose et al., 1996 556 women with 26 751 first visit Self-administered AOR (95% CI) Age, first-visit year, Results for
first diagnosis, outpatients aged questionnaire drinking, physical nonsmoking
Aichi Cancer histologically ≥20 without ever Husband nonsmoker 1 activity women
Center, confirmed cervical being diagnosed
Japan cancer with cancer Husband smokes 1.3 (1.07-1.59)
1996
Husband smokes 1.0 (0.76-1.33)
<20 cig/day

Husband smokes 1.55 (1.24-1.94)


≥20 cig/day

Coker et al., 2002 High-grade SIL 427 controls with Interviewed by HSIL: 1 Age, age at first Not restricted
(HSIL) cases, 313 mean age near 28 telephone No passive smoking sexual intercourse, to nonsmokers.
South Carolina low-grade SIL years; response (PS) by either parent/ race, HR-HPV High grade
Health Department, (LSIL) cases, with rate 72.5% sex partner status, and active squamous
1995-1998 mean age near 25 smoking intraepithelial
years; response PS by either parent/ 2.2 (1.0-4.8) lesion.
rate 82.1% sex partner

No PS by parent as 1
a child

PS by parent as a 1.9 (1.0-3.7)


child

No PS by sex partner 1

PS by sex partner 1.0 (0.5-2.1)

No PS 1

1-9 yrs of PS 0.7 (0.2-2.6)

10+ yrs of PS 1.8 (0.9-3.6)

LSIL: 1 Low grade


No PS by either parent squamous
or sex partner intraepithelial
lesion
PS by either parent or 1.4 (1.0-2.0) PS refers to
sex partner passive smoking
Health effects of exposure to secondhand smoke (SHS)

37
38
Table 2.6b Exposure to SHS and cervical cancer - Case-control studies

Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)*
confounders
Coker et al., 2002 No PS by parent as 1
a child
1995-1998
PS by parent as a 1.2 (0.9-1.7)
child

No PS by sex partner 1

PS by sex partner 1.1 (0.8-1.5)


IARC Handbooks of Cancer Prevention

Never PS 1

1-9 yrs of PS 1.8 (1.1-3.0)

10+ yrs of PS 1.4 (0.9-2.0)

Wu et al., 2003 100 histologically 197 women age Nurse No childhood, home 1 Age and residence- Results for
confirmed women (±2 yrs) and interviewer- ETS exposure matched, education, nonsmoking
Taiwan (CIN2: 39, CIN3:12, residence matched administered # pregnancies, age women
1999-2000 CIS: 46, invasive with negative Pap questionnaire Childhood, home ETS 0.99 (0.54-1.83) at first intercourse,
cancer: 3) aged ≥19 smears exposure cooking ventilation ETS refers to
environmental
No childhood, work 1 tobacco smoke
ETS exposure ETS refers to
environmental
Childhood, work ETS 1.03 (0.47-2.26) tobacco smoke
exposure

No adulthood, home 1
ETS exposure

Adulthood, home ETS 2.73 (1.31-5.67)


exposure

No adulthood, work 1
ETS exposure

Adulthood, work ETS 1.56 (0.83-2.92)


exposure

Lifetime, childhood,
home ETS exposure

No 1

1-10 cig/day 1.35 (0.78-2.35)

>10 cig/day 1.02 (0.43-2.40)


Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)*
confounders
Wu et al., 2003 Lifetime, childhood,
work ETS exposure
Taiwan
1999-2000 No 1

1-10 cig/day 1.25 (0.54-2.90)

>10 cig/day 0.79 (0.24-2.55)

Lifetime, childhood,
home ETS exposure

No 1

1-10 cig/day 1.11 (0.59-2.09)

>10 cig/day 0.82 (0.31-2.19)

Lifetime, childhood,
work ETS exposure

No 1

1-10 cig/day 1.34 (0.53-3.36)

>10 cig/day 0.79 (0.21-2.97)

Lifetime, adulthood,
home ETS exposure

No 1

1-10 cig/day 2.13 (0.96-4.73)

>10 cig/day 3.97 (1.65-9.55)

Lifetime, adulthood,
work ETS exposure

No 1

1-10 cig/day 1.47 (0.64-3.37)

>10 cig/day 1.65 (0.73-3.75)

Lifetime, adulthood, all


ETS exposure

No 1

1-10 cig/day 1.90 (0.72-5.03)

>10 cig/day 2.99 (1.10-8.09)


Health effects of exposure to secondhand smoke (SHS)

39
40
Table 2.6b Exposure to SHS and cervical cancer - Case-control studies

Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)*
confounders
Sobti et al., 2006 103 histologically 103 controls free of Interviewer- GSTM1 null: ORs calculated
confirmed cervical any cancer administered Never smoker 1 from table
India cancer patients questionnaire Passive smoker 6.95

GSTM1 present: GSTM1 gene


Never smoker 1 (glutathione
Passive smoker 4.32 S-Transferese
mu1)
GSTT1 null: GSTT1
IARC Handbooks of Cancer Prevention

Never smoker 1 (glutathione


Passive smoker 28.57 S-transferese
theta1)
GSTM1 present:
Never smoker 1
Passive smoker 3.72

GSTP1 ile/ile:
Never smoker 1
Passive smoker 4.33

GSTP1 ile/val: GSTP1 gene


Never smoker 1 (glutathione S-
Passive smoker 5.53 transferese pi1)

GSTP1 val/val:
Never smoker 1
Passive smoker 5.13

Tsai et al., 2007 Women aged ≥20 Randomly selected Interviewer- Inflammation: 1 Age, education, Results for
screened by PAP from women with administered Non-smoker times of prior Pap nonsmoking
Taiwan smear with CIN I negative Pap smear questionnaire smear, # of lifetime women
2003-2005 or over for the first findings, matched Secondhand smoker 1.3 (0.6-2.7) sexual partners, age
time on residence at first intercourse,
and agreeing to Nonsmoker 1 family history
interview cervical cancer,
Lifetime 1-10 pack/yrs 0.9 (0.4-1.9) cooking oil fume
exposure, HPV
Lifetime 11-20 1.7 (0.5-5.6) infection
pack/yrs

Lifetime >20 pack/yrs 4.1 (1.3-12.5)

CIN1: 1 CIN (Cervical


Nonsmoker Intra-epithelial
neoplasia grade
SHS 1.6 (0.8-3.2) 1)

Nonsmoker 1
Adjustment
Reference, Characteristics of Characteristics of Exposure Relative risk
Exposure categories for potential Comments
location, period cases controls assessment (95% CI)
confounders
Lifetime 1-10 pack/yrs 1.3 (0.6-2.8)
Tsai et al., 2007
Lifetime 11-20 2.4 (0.7-7.7)
Taiwan pack/yrs
2003-2005
Lifetime >20 pack/yrs 4.0 (1.2-13.8)

≥CIN2: 1 CIN2 (Cervical


Nonsmoker Intra-epithelial
neoplasia grade
Secondhand smoker 1.8 (0.9-4.1) 2)

Nonsmoker 1

Lifetime 1-10 pack/yrs 1.3 (0.6-2.9)

Lifetime 11-20 2.1 (0.6-7.9)


pack/yrs

Lifetime >20 pack/yrs 7.2 (2.5-20.6)


Health effects of exposure to secondhand smoke (SHS)

41
IARC Handbooks of Cancer Prevention

cancer among women (Slattery et


al., 2003).

Esophageal cancer

This review identified one published


study examining the relationship
between SHS exposure and
esophageal cancer (Wang et al.,
2006). The researchers conducted a
population based case-control study
in 107 esophageal squamous cell
carcinoma cases and 107 controls
matched on residency, age, and sex
in five townships of Huaian, China.
They found that exposure to SHS was
associated with an increased risk of
esophageal cancer (OR=2.04; 95%
Figure 2.3 Pooled risk estimates from random effects meta-analysis of
CI=1.14-3.70). However, these results
exposure to SHS and cervical cancer
were not restricted to nonsmokers.
Trimble et al., 2005a and 2005b refer to estimates from the 1963 and 1975 cohorts respectively. All data included in
the reference Trimble et al., 2005
Liver cancer
Risk estimates are plotted in Figure risk for HPV infection indirectly
2.3 for the most comprehensive associated with SHS exposure. The relationship between passive
SHS exposure index available. smoking and risk for cancer of the
Since several studies presented Colorectal cancer liver has also been investigated. A
risk estimates stratified by mutually prospective cohort study conducted
exclusive exposure categories Several recent studies, addressing in 160 130 Korean women, aged 40-
(Hirayama, 1984; Slattery et al., genetic markers of risk, have 88, found no association between
1989; Coker et al., 1992; Hirose examined the relationship between liver cancer and husbands’ smoking
et al., 1996; Wu et al., 2003; Tay passive smoking and colorectal habit (Jee et al., 1999). There were
& Tay, 2004; Tsai et al., 2007), cancer. It was found that passive 83 cases of liver cancer identified
these estimates were pooled using smoking was associated with an in the follow-up period from July,
random effects meta-analysis. increased risk for colorectal cancer 1994 to December, 1997. Wives
Although a combined random effects only among NAT2 fast acetylators with former smoking husbands had
estimate is shown, none of these (OR=2.6; 95% CI=1.1-5.9) for ex- RR=0.8 (95% CI=0.5-1.5) and wives
studies adequately accounted for posure in childhood and adulthood of current smoking husbands had
prior human papillomavirus (HPV) (Lilla et al., 2006). After adjusting RR=0.7 (95% CI=0.4-1.1). Another
infection. Consequently, the evidence for active smoking, total long-term cohort study conducted in Japanese
is not informative as to whether exposure to passive smoke was found nonsmoking women, found an
SHS increases the risk of cervical to be associated with increased risk elevated, but not significant, age-
cancer in HPV-infected women. of rectal cancer among men exposed adjusted risk of liver cancer after nine
Overall, increased risk was found to >10 hours/week compared to none years of follow-up (OR=1.2; 95%
in association with SHS exposure (OR=1.4; 95% CI=1.0-2.1), but no CI=0.45-3.2) (Nishino et al., 2001);
(Figure 2.3). However, the increase significant associations were found however, there were only 20 cases
cannot be separated from increased between exposure to SHS and rectal of liver cancer. It was hypothesised

42
Health effects of exposure to secondhand smoke (SHS)

that parental smoking during SHS exposure and risk of nasal sinus for age and education (OR=1.1; 95%
pregnancy might plausibly increase cancer. Only three studies were found CI=0.4-3.0) (Sandler et al., 1985a).
risk for childhood hepatoblastoma by (Hirayama, 1984; Fukuda & Shibata, Another case-control study found
exposing the fetus’ liver through the 1990; Zheng et al., 1993) with up that neither exposure to maternal nor
fetal circulation (Pang et al., 2003). to a three-fold increase in nasal paternal smoking during childhood
Though there were only 10 cases, sinus cancer risk associated with was associated with an unadjusted
they found a significantly elevated SHS exposure (Tables 2.7a,b). The risk of cancer of the lip, oral cavity, and
OR of developing hepatoblastoma report concluded that the evidence pharynx (maternal smoking OR=0.8;
associated with smoking by both regarding SHS exposure and nasal 95% CI=0.2-3.5, paternal smoking
parents (OR=4.74; 95% CI=1.68-13.35). sinus cancer was suggestive, but not OR=1.3; 95% CI=0.4-3.8) (Sandler et
An increased risk of hepatoblastoma sufficient to infer a causal relationship, al., 1985b). Neither of these studies
was also reported if both parents and that more studies by histological was limited to never smokers.
smoked relative to neither parent type and subsite were needed. New
smoking (RR=2.28; 95% CI=1.02-5.09) studies were not found. Ovarian cancer
(Sorahan & Lancashire, 2004).
Nasopharyngeal cancer A cohort study conducted in Japanese
Lymphoma nonsmoking women, found an
The 2006 US Surgeon General’s elevated, but not significant, increased
Only one study has been published report on involuntary smoking also risk of ovarian cancer associated
examining the relationship between addressed SHS exposure and the with husbands smoking status after
SHS exposure and cancer of the risk of nasopharyngeal cancer. adjusting for age (OR=1.7; 95%
lymph nodes in adults. A population- Only three studies were found in the CI=0.58-5.2) (Nishino et al., 2001).
based case-control study was literature (Yu et al., 1990; Cheng et However, there were only 15 cases of
conducted examining the association al., 1999; Yuan et al., 2000) showing ovarian cancer reported during nine
between SHS exposure and Hodgkin slightly elevated related relative risks. years of follow-up for 9675 women. A
lymphoma (HL) among US women The US Surgeon General’s report population-based case-control study
aged 19-44 years and those aged concluded that though biologically in the USA, examined the hypothesis
45-79 years (Glaser et al., 2004). plausible, the evidence regarding that active and passive tobacco
Though not limited to never smokers, SHS exposure and nasopharyngeal smoking are associated with the risk of
exposure to SHS during childhood cancer was inadequate to infer a epithelial ovarian cancer (558 women
was significantly associated with risk causal relationship. Since this review, with epithelial ovarian cancer and
of HL in the 19-44 year age group no new studies have been published 607 population controls) (Goodman &
(OR=1.6; 95% CI=1.03-2.4) after in the literature regarding SHS Tung, 2003). Significant associations
adjusting for age, race, having a single exposure and risk of nasopharyngeal were not found among never smokers
room at 11 years, birth place (USA cancer (Table 2.8). with exposure to passive smoke
vs. other), renting a house/dwelling from either parent for gestational
at age eight, being Catholic, and Oral cancer or childhood exposure. In a study
ever breastfeeding. Exposure to SHS among never smokers (434 cases
during adulthood was not significantly Few studies have examined the role and 868 age and region matched
associated with risk of HL (adjusted of SHS in the etiology of oral cancer. hospital controls), a decreased risk
OR=0.8; 95% CI=0.6-1.2). In a case-control study of overall of ovarian cancer was found to be
cancer and adult exposure to passive associated with daily exposure to
Nasal sinus cancer smoking, it was found that exposure passive smoke (OR=0.68; 95%
to passive smoke was not significantly CI=0.46-0.99) (Baker et al., 2006).
The 2006 Surgeon General’s report associated with cancer of the lip, oral
on involuntary smoking addressed cavity, and pharynx after adjusting

43
44
Table 2.7a Exposure to SHS and nasal sinus cancer - Cohort study

Reference, Relative risk Adjustment for


Cohort description Exposure assessment Exposure categories
location, period (95% CI) potential confounders

Hirayama et al., 1984 91 540 nonsmoking, married Interviewer-administered Husband’s smoking: RR (90% CI) Husband’s age
women, aged ≥40 years (28 questionnaire
Japan deaths due to nasal sinus None 1
1966-1981 cancer)
1-14 cig/day 1.67 (0.67-4.20)

15-19 cig/day 2.02 (0.64-6.33)

≥ 20 cig/day 2.55 (1.04-6.27)


IARC Handbooks of Cancer Prevention

Table 2.7b Exposure to SHS and nasal sinus cancer - Case-control study

Relative risk Adjustment


Reference, Characteristics of Exposure
Characteristics of cases Exposure categories (95% CI) or odds for potential
location, period controls assessment
ratio confounders

Fukuda & Shibata, 1990 46 women 40-79 years with 88 population controls, Self-administered Among nonsmokers: none
incident neoplasms of the individually matched questionnaire
Japan maxillary sinuses; 96.6% on age, gender, and No smokers in 1
1982-1986 response rate health-center region; household
93.4% response rate
1 smoker in household 1.40 (0.57-3.49)

>1 smoker in household 5.73 (1.58-20.73)

Zheng et al., 1993 147 deaths from nasal sinus 449 White controls Questionnaire Nonsmoker in household 1
cancer in White males aged aged ≥45 years who sent to next of kin
USA ≥45 years who participated in died from other causes Smoking spouse 3.0 (1.0-8.9) age, alcohol
1986 the 1986 US National Mortality
Followback Survey Smoking spouse,
maxillary sinus cancers 4.8 (0.9-24.7) age, alcohol
Table 2.8 Exposure to SHS and nasopharyngeal cancer - Case-control studies

Adjustment
Reference, Characteristics of Exposure Relative risk
Characteristics of cases Exposure categories for potential
location, period controls assessment (95% CI)
confounders

Yu et al., 1990 306 patients <50 306 population controls, Interviewer- Among nonsmokers: Age and gender
years old with incident individually matched administered
China nasopharyngeal on age, gender, questionnaire Never exposed to SHS 1
1983-1985 carcinoma; 100% and neighborhood; at home
response rate response rate not
stated Father smoked when 0.6 (0.3-1.2)
subject was age 10

Mother smoked when 0.7 (0.3-1.5)


subject was age 10

Other household 1.0 (0.5-2.2)


members smoked when
subject was age 10

Lived with any smoker at 0.7 (0.4-1.3)


age 10

Spouse smoked 0.8 (0.4-1.9)

Ever exposed to SHS at 0.7 (0.4-1.4)


home

Cheng et al., 1999 375 histologically 327 healthy community Questionnaire Nonsmokers: Age, sex, education,
confirmed incident controls individually family history of
Taiwan nasopharyngeal cancers matched to cases on No childhood SHS 1 NPC
1991-1994 (NPC),≤75 years old, no sex, age and residence;
previous NPC, residence 88% response rate Childhood SHS 0.6 (0.4-1.0)
in Taipei last 6 months;
99% response rate No adulthood SHS 1

Adulthood SHS 0.7 (0.5-1.2)

Yuan et al., 2000 935 histologically 1032 persons from the In-person interview Male and female Age, sex, education,
confirmed community frequency by 4 trained nonsmokers: preserved foods,
China nasopharyngeal cancers; matched by age interviewers citrics, cooking
1987-1991 84% response rate (± 5 yrs) and sex employing smoke, occupational
a structured exposure to
questionnaire chemical fumes,
history of chronic
ear, nose condition,
family history of
NPC
Health effects of exposure to secondhand smoke (SHS)

45
46
Table 2.8 Exposure to SHS and nasopharyngeal cancer - Case-control studies

Adjustment
Reference, Characteristics of Exposure Relative risk
Characteristics of cases Exposure categories for potential
location, period controls assessment (95% CI)
confounders
Yuan et al., 2000 Never exposed over 1
lifetime
China
1987-1991 Mother smoked 2.30 (1.23-4.28)

Mother smoked 1.65 (0.83-3.29)


<20 cig/day

Mother smoked 4.24 (1.84-9.77)


IARC Handbooks of Cancer Prevention

≥20 cig/day

Father smoked 1.99 (1.18-3.35)

Father smoked 1.73 (0.99-3.02)


<20 cig/day

Father smoked 2.28 (1.31-3.99)


≥20 cig/day

Non-parental household 2.37 (1.20-4.71)


member smoked

Any household member 2.05 (1.22-3.44)


smoked

Total household 1.78 (1.02-3.13)


<20 pack-yrs

Total household 2.23 (1.28-3.89)


20-39 pack-yrs

Total household 2.51 (1.18-5.34)


40+ pack-yrs

Spouse smoked 2.48 (1.42-4.31)

Spouse smoked 2.37 (1.28-4.41)


<20 yrs

Spouse smoked 2.59 (1.38-4.84)


20+ yrs

Spouse smoked 2.44 (1.35-4.42)


<20 cig/day

Spouse smoked 2.52 (1.36-4.65)


20+ cig/day

Spouse <20 pack-yrs 2.47 (1.37-4.45)


Adjustment
Reference, Characteristics of Exposure Relative risk
Characteristics of cases Exposure categories for potential
location, period controls assessment (95% CI)
confounders
Yuan et al., 2000 Spouse 20-39 pack-yrs 2.12 (1.07-4.19)

China Spouse 40+ pack-yrs 4.69 (1.60-13.70)


1987-1991
Non-spousal household 1.86 (1.09-3.18)
member smoked

Any household member 1.88 (1.12-3.16)


smoked

Total household smoked 1.81 (1.03-3.19)


<20 cig/day

Total household smoked 1.70 (0.97-2.98)


20-39 cig/day

Total household 2.72 (1.39-5.31)


40+ cig/day

Co-worker smoked 1.99 (1.19-3.32)

Co-worker smoked 1.76 (1.03-3.02)


<3 hrs

Co-worker smoked 2.28 (1.32-3.93)


3+ hrs
Health effects of exposure to secondhand smoke (SHS)

47
IARC Handbooks of Cancer Prevention

The authors hypothesised that


immunosuppression by nicotine
or upregulation of enzymes that
metabolise carcinogens may be
responsible for the protective effects
observed.

Pancreatic cancer

For pancreatic cancer, the literature


review identified both cohort and
case-control studies (Tables 2.9a,b).
The three cohort studies provided
no evidence for increased risk of
pancreatic cancer associated with
the exposure indicators (Nishino et
al., 2001; Gallicchio et al., 2006).
The case-control studies also
provided little evidence for increased
risk, except for one study carried Figures 2.4 Pooled risk estimates from random effects meta-analysis of
out in Egypt (Lo et al., 2007). This exposure to SHS and pancreatic cancer
hospital-based case-control study Gallicchio et al., 2006a and 2006b refer to estimates from the 1963 and 1975 cohorts respectively.
All data included in the reference Gallicchio et al., 2006
used two institutions to identify the
cases and drew controls from the
otolaryngology and ophthalmology significantly associated with risk of of follow-up (Nishino et al., 2001). The
inpatient services; most cases did stomach cancer; the ORs associated age-adjusted RR for stomach cancer
not have histological confirmation with husband being an ex-smoker or associated with husband’s smoking
and there is concern about the of smoking 1-19 cigarettes/day was was 0.95 (95% CI=0.58-1.6).
comparability of cases and controls, 1.03 (90% CI=0.89-1.18) and for 20+ Two case-control studies
given the methods of recruitment. cigarettes/day, OR=1.05 (90% CI=0.89- examined the relationship between
The pooled estimate calculated by 1.24). Another prospective cohort SHS exposure and risk of stomach
the Working Group for exposure at study conducted in Korean women cancer. Using information on 65
home as an adult was OR=1.35 (95% aged 40-88 years, examined the incident stomach cancer cases
CI=0.88-2.07) (Figure 2.4). association between SHS exposure and 343 population controls,
from the husband’s smoking and risk identified between 1994 and 1997
Stomach cancer of stomach cancer (Jee et al., 1999). in Canada, it was found that among
It was found that neither husband’s male never smokers there was a
The relationship between exposure former smoking (OR=1.0; 95% CI=0.7- strongly increased risk associated
to SHS and cancer of the stomach 1.5) nor current smoking (OR=0.9; with residential and occupational
has been investigated in five study 95% CI=0.6-1.2) were associated with exposure to SHS among subjects
populations (Tables 2.10a,b). In risk of stomach cancer in their wives. with cardial stomach cancer (Mao
a cohort of 91 540 nonsmoking Also examined was the association et al., 2002). For men with cardial
Japanese women ≥40 years, followed between SHS and stomach cancer cancer, the ORs ranged from 2.5
from 1966 to 1981, there were 854 in a population-based prospective (95% CI=0.5-13.1) for 1-55 lifetime
cases of stomach cancer (Hirayama, study among Japanese women aged person-years of exposure, to OR=4.5
1984). Husband’s smoking was not 40 years and older during nine years (95% CI=0.9-21.8) for 56-125 lifetime

48
Health effects of exposure to secondhand smoke (SHS)

person-years of exposure to SHS,

this article; men

this article; men


SHS exposure

SHS exposure
Comments

cohort studies

cohort studies
excluded from

excluded from
Two separate

Two separate
after controlling for 10 year age

described in

described in
group; province; education; social

analyses

analyses
class; and meat, fruit, vegetable, and
juice consumption. Among never
smoking men, the adjusted ORs
were lower for the distal subsite of
confounders
for potential
Adjustment

Age, education,

Age, education,
stomach cancer than cardia. In a

marital status

marital status
case-control study based in the USA,
it was found that the unadjusted RR
Age

for digestive cancer associated


with father’s smoking was 1.7
(95% CI=0.8-3.9), and for maternal
1.2 (0.45-3.2)
Relative risk

0.9 (0.4-2.3)
1.1 (0.4-2.8)
(95% CI)

smoking, RR=0.6 (95% CI=0.2-2.1)


1

1
(Sandler et al., 1985b). In the same
study population, the researchers
found the RR for digestive cancer
associated with spousal smoking
No household members

No household members
Any household member

Any household member


Exposure categories

to be 1.0 (95% CI=0.5-2.2) after


Husband does not

Husband smokes

adjusting for age and education


(Sandler et al., 1985a).
smokes

smokes
smoke

smoke

smoke

Childhood cancers
Table 2.9a Exposure to SHS and pancreatic cancer - Cohort studies

Childhood leukemia
Self-administered

Self-administered

Self-administered
assessment
Exposure

The 2006 US Surgeon General’s


questionnaire

questionnaire

questionnaire

report on SHS summarised the


evidence on childhood leukemia
and SHS exposure. The report
concluded that the evidence was
women ≥40 years at enrollment (19

suggestive, but not sufficient to


(22 pancreatic cancer cases) with
pancreatic cancer cases) with no

pancreatic cancer cases) with no

infer a causal relationship between


18 839 never smoking adults
previous diagnosis of cancer
9675 never smoking married

20 181 never smoking adults


≥25 years at enrollment (34
Cohort description

prenatal and postnatal exposure to


no prior cancer diagnosis
≥25 years at enrollment

SHS and childhood leukemia. Since


prior cancer diagnosis

this report, three new studies have


been published on SHS and risk of
childhood leukemia. The relationship
between parental smoking and
childhood leukemia in the Northern
California Childhood Leukemia Study
Nishino et al., 2001
location, period

was investigated (Chang et al., 2006).


Gallicchio et al.,
Reference,

Maryland, USA

Maryland, USA
1984-1992

1975-1994
1963-1978
Japan

2006

49
50
Table 2.9b Exposure to SHS and pancreatic cancer - Case-control studies

Adjustment
Reference, Characteristics of Characteristics of Exposure Exposure Relative
for potential Comments
location, period cases controls assessment categories risk(95% CI)
confounders

Villeneuve et al., 105 never-smoking 1145 adult population Self-administered Never exposed to 1 Age, BMI,
2004 adults ≥30 years with controls, matched questionnaire SHS income,
pancreatic cancer; on province and province, sex
Canada female response rate: frequency matched SHS exposure at 1.37 (0.46-4.07)
1994-1997 56%; male response on age and gender; home or work up to
rate: 55% female response rate: age 19
71%; male response
rate: 65% SHS exposure at 1.01 (0.41-2.50)
home or work during
IARC Handbooks of Cancer Prevention

adulthood

SHS exposure at 1.21 (0.60-2.44)


home or work in
lifetime

1-20 yrs SHS 0.97 (0.42-2.26)


exposure at home

21-34 yrs SHS 0.90 (0.39-2.11)


exposure at home

35+ yrs SHS 1.43 (0.66-3.11)


exposure at home

All: 1-9 yrs SHS 1.55 (0.68-3.56)


exposure at work

10-21 yrs SHS 1.16 (0.49-2.74)


exposure at work

22+ yrs SHS 1.20 (0.54-2.67)


exposure at work

SHS exposure only 0.97 (0.43-2.18)


at home

SHS exposure only 1.43 (0.61-3.36)


at work

1-35 yrs SHS 1.33 (0.60-2.93)


exposure at home or
work

36-56 yrs SHS 1.09 (0.49-2.41)


exposure at home or
work

57+ yrs SHS exposure 1.15 (0.54-2.47)


at home or work
Adjustment
Reference, Characteristics of Characteristics of Exposure Exposure Relative
for potential Comments
location, period cases controls assessment categories risk(95% CI)
confounders
Hassan et al., 2007 735 patients with 805 visitors who Interviewer- Nonsmokers: 1 Age, sex, 294
newly diagnosed, accompanied cancer administered Never exposed to race, diabetes, nonsmoking
Texas, USA histologically- patients (usually questionnaire SHS alcohol cases
2000-2006 confirmed pancreatic spouses), frequency consumption, and 412
adenocarcinoma matched on age, race, Ever exposed to 1.1 (0.8-1.6) education, state nonsmoking
who were English and sex SHS (childhood or of residence, controls
speaking US citizens adulthood) marital status

Occasional SHS 0.9 (0.5-1.6)


exposure during
childhood

Regular SHS 1.1 (0.7-1.6)


exposure during
childhood

Occasional SHS 1.4 (0.7-2.5)


exposure at home
during adulthood

Regular SHS 1.03 (0.7-1.6)


exposure at home
during adulthood

Occasional SHS 0.8 (0.5-1.3)


exposure at work
during adulthood

Regular SHS 1.2 (0.7-1.9)


exposure at work
during adulthood

SHS exposure only 1.2 (0.7-1.9)


during childhood

SHS exposure only 1.3 (0.8-2.2)


during adulthood

SHS exposure during 1.0 (0.6-1.5)


both childhood and
adulthood

1-5 yrs SHS exposure 0.6 (0.2-1.7)


during childhood

6-10 yrs SHS 0.6 (0.2-1.5)


exposure during
childhood

>10 yrs SHS exposure 1.1 (0.7-1.6)


during childhood
Health effects of exposure to secondhand smoke (SHS)

51
IARC Handbooks of Cancer Prevention

This case-control study included 327

cases and 97
Comments

nonsmoking

nonsmoking
acute childhood leukemia cases

controls
(281 acute lymphoblastic leukemia

41
(ALL) and 46 acute myeloid leukemia
(AML)) and 416 controls matched
confounders
for potential
Adjustment

on age, sex, maternal race, and

rural/urban
residence
Hispanic ethnicity. The investigators

Age, sex,
found that maternal smoking was not
associated with an increased risk of
either ALL (OR=1.12; 95% CI=0.79-
Relative risk

6.0 (2.4-14.8)
1.1 (0.6-2.01)

1.2 (0.8-1.9)

0.8 (0.4-1.6)

1.2 (0.8-1.8)
1.1 (0.7-1.7)
1.59) or AML (OR=1.00; 95% CI=0.41-
1 (0.5-1.7)
(95% CI)

2.44). The OR for AML associated

1
with paternal preconception smoking
was 3.84 (95% CI=1.04-14.17). The
corresponding OR for ALL associated
>20 yrs SHS exposure

>20 yrs SHS exposure


with paternal preconception smoking

Never lived with a


categories

during adulthood
Exposure

Ever lived with a


exposure during

exposure during

exposure during

exposure during

was 1.32 (95% CI=0.86-2.04).

smoker, <30 yrs


Nonsmokers:
11-20 yrs SHS

11-20 yrs SHS

during lifetime
1-10 yrs SHS

1-10 yrs SHS

The role of maternal alcohol and


adulthood

adulthood

coffee consumption and parental

smoker
lifetime

lifetime

smoking on the risk of childhood


acute leukemia was investigated in
a multicenter, hospital-based, case-
Table 2.9b Exposure to SHS and pancreatic cancer - Case-control studies

assessment

control study in France with 280


Exposure

questionnaire
administered

incident cases and 288 hospitalised


Interviewer-

controls, frequency matched with the


cases by age, gender, and center
(Menegaux et al., 2005). Significant
associations of maternal smoking
throat, ophthalmology
Characteristics of

194 hospital controls

matched on age and

with ALL (OR=1.1; 95% CI=0.7-1.6)


from the ear/nose/

units frequency-
controls

and acute non-lymphocytic leukemia


(ANLL) (OR=1.0; 95% CI=0.5-2.1)
were not found. Paternal smoking
was also not significantly associated
sex

with risk of ALL (OR=1.1; 95%


diagnosed pancreatic

CI=0.7-1.5) or ANLL (OR=1.3; 95%


Characteristics of

CI=0.6-2.7). Another case-control


194 adults 19-90
years with newly
cases

study was conducted in France of


coffee, alcohol, SHS, and risk of
cancer

acute leukemia (Menegaux et al.,


2007). The researchers identified 472
cases of childhood acute leukemia
Hassan et al., 2007
location, period

(407 ALL and 62 with AML) and


Reference,

frequency-matched 567 population


Lo et al., 2007
Texas, USA
2000-2006

2001-2004

controls by age, sex, and region


of residence. Only the risk of ALL
Egypt

associated with maternal smoking

52
Health effects of exposure to secondhand smoke (SHS)

during pregnancy was significantly

Confidence intervals not provided


Husband’s age and occupation.
elevated (OR=1.4; 95% CI=1.0, 1.9),

Husband’s age and occupation


Adjustment for potential
after adjusting for age, gender, region,

confounders
socio-professional category, and
birth order. Paternal smoking before,
during, or after pregnancy was not

Husband’s age
significantly associated with risk of
either ALL or AML. These new studies
provide more evidence suggesting a
causal relationship between prenatal
and postnatal exposure to SHS and

1.05 (0.89-1.24)
1.00 (0.81-1.22)
1.00 (0.86-1.17)

1.03 (0.89-1.18)
1.15 (0.93-1.43)

1.01 (0.86-1.19)
Relative risk

RR (90% CI)
childhood leukemia.

(95% CI)

0.99
1.02
1

1
Childhood brain cancer

The US Surgeon General (U.S.

Husband is ex-smoker or

Husband is ex-smoker or
Department of Health and Human
Exposure categories

Husband is ex-smoker
Nonsmoking husband

Nonsmoking husband

Nonsmoking husband
Services, 2006), the California EPA

smokes 1-19 cig/day

smokes 1-19 cig/day


Husband smokes

Husband smokes

Husband smokes

Husband smokes

Husband smokes
(California Environmental Protection

15-19 cig/day
Agency: Air Resources Board, 2005),

1-14 cig/day
≥20 cig/day

≥20 cig/day

≥20 cig/day
and the IARC (2004) publications have
reviewed the evidence relating the
risk of childhood brain tumors (CBTs)
to SHS exposure. In addition to the
Exposure assessment

Interviewer-administered

Interviewer-administered

studies presented in these reports,


Table 2.10a Exposure to SHS and stomach cancer - Cohort studies

the effect of parental smoking on the


risk of CBT was examined in a small
questionnaire

questionnaire

hospital-based case-control study


in China (Hu et al., 2000). Parents
of 82 children with newly diagnosed
primary malignant brain tumors
≥40 years (854 deaths due

were individually matched to 246


≥40 years (716 deaths due
Cohort description

hospital controls from 1991 to 1996.


91 540 nonsmoking,

91 540 nonsmoking,
to stomach cancer)

to stomach cancer)

There was little evidence to support


married women

married women

an association between parents’


smoking before or during pregnancy
and risk of CBT. More recently,
the association between CBTs (all
histological types combined) and
exposure of parents and children to
location, period

cigarette smoke was evaluated in a


Reference,

comprehensive, large, international


Hirayama, 1984
Hirayama, 1981

case-control study (Filippini et al.,


1966-1981
1966-1979

2002).
Japan

Japan

53
54
Table 2.10a Exposure to SHS and stomach cancer - Cohort studies

Reference, Relative risk Adjustment for potential


Cohort description Exposure assessment Exposure categories
location, period (95% CI) confounders

Jee et al., 1999 157 436 nonsmoking, Self-administered Husband never smoked 1 Age, husband’s age, SES,
married women questionnaire residence, husband’s vegetable
South Korea ≥40 years (197 stomach consumption, husband’s
1994-1997 cancer cases) occupation
Husband is ex-smoker 1.0 (0.7-1.5)

Husband is current smoker 0.9 (0.6-1.2)


IARC Handbooks of Cancer Prevention

Nishino et al., 2001 9675 nonsmoking women Self-administered Nonsmoking husband 1 Age
≥40 years (83 stomach questionnaire
Japan cancer cases) Husband smokes 0.95 (0.58-1.6)
1984-1992
Neither husband nor other 1
household members
smoke

Other household members 0.90 (0.52-1.5)


smoke (and husband does
not smoke)

Husband smokes (and 0.91 (0.48-1.7)


other household members
do not smoke)

Husband and other 0.90 (0.45-1.8)


household members
smoke

Nonsmoking husband 1
Age, study area, alcohol
consumption, vegetable intake,
fruit intake, miso soup intake,
pickled vegetable intake
Husband smokes 0.98 (0.59-1.6)

No other household 1
member smoke

Other household members 0.87 (0.54-1.4)


smoke
Table 2.10b Exposure to SHS and stomach cancer - Case-control studies

Adjustment
Reference, Characteristics Characteristics Exposure Exposure Relative risk
for potential Comments
location, period of cases of controls assessment categories (95% CI)
confounders
Sandler et al., 518 cancer 518 friend and Self-administered Nonsmoking spouse 1 Age and education Only 39 patients
1985a patients 15-59 community questionnaire or never married 15-59 years with
years; 72% controls cancer of the
North Carolina, USA response rate individually Spouse smoked 1.0 (0.5-2.2) digestive system
1979-1981 matched on regularly (at least 1 and 489 controls
gender, age cig/day for at least used
and race; 75% 6 months) any time
response rate during marriage

Sandler et al., 470 cancer cases 438 controls, Self-administered Not exposed to SHS 1 None 31 digestive cancer
1985b (any site); 70% individually questionnaire from mother during cases were used in
overall response matched on first 10 yrs of life the SHS analysis
North Carolina, USA rate gender, age and and all of the
1979-1981 race SHS exposure from 0.7 controls; results
mother during first for nonsmokers
10 yrs of life presented; no CIs
provided
Not exposed to SHS 1
from father during
first 10 yrs of life

SHS exposure from 1.3


father during first 10
yrs of life

Mao et al., 2002 1171 cases of 207 population Self-administered Cardial stomach Age, province, Only never smoking
newly diagnosed, controls; 62.6% questionnaire cancer: education, social men were used for
Canada histologically overall response Never exposed 1 class, meat, the SHS exposure
1994-1997 confirmed cardial rate to SHS at work or vegetable, fruit and analysis
or distal stomach home juice consumption
cancers; 63.2%
overall response 1-22 yrs SHS 3.5 (0.7-17.3)
rate exposure at home
or work

23-42 yrs SHS 2.8 (0.5-14.2)


exposure at home
or work

43+ yrs SHS 5.8 (1.2-27.5)


exposure at home
or work

1-55 smoker-yrs of 2.5 (0.5-13.1)


SHS exposure at
home or work
Health effects of exposure to secondhand smoke (SHS)

55
IARC Handbooks of Cancer Prevention

The study sample consisted of 1218


Comments cases <20 years old and newly
diagnosed with CBT and 2223
population-based controls. There
was no association between the
risk of CBT and mothers’ smoking
(OR=0.9; 95% CI=0.8-1.0) or paternal
confounders

smoking (OR=1.1; 95% CI=0.9-1.2)


for potential
Adjustment

prior to pregnancy, mother smoking


during pregnancy (home or work)
(OR=0.9; 95% CI=0.8-1.1), or
SHS exposure of the child during
the first year of life (OR=1.0; 95%
Relative risk

4.5 (0.9-21.8)

3.4 (0.7-17.0)

1.0 (0.5-2.0)
0.9 (0.5-1.7)

0.6 (0.3-1.3)

0.7 (0.3-1.4)

1.1 (0.6-2.0)
0.5 (0.2-1.1)

CI=0.8-1.1). The findings did not


(95% CI)

change after adjusting for the child’s


1

age, histological type, or location.


There was some variation across
histological type. For example, risk of

of exposure at home
43+ yrs exposure at
23-42 yrs exposure
of SHS exposure at

126+ smoker-yrs of

126+ smoker-yrs of
the primitive neuroectodermal tumors
1-55 smoker-yrs of
56-125 smoker-yrs

56-125 smoker-yrs
exposure at home

exposure at home
Never exposed to
SHS at work or at
SHS exposure at

Distal stomach

at home or work
categories
Exposure

was significantly elevated in children


home or work

home or work

home or work
1-22 yrs SHS

who were regularly exposed during

exposure
cancer:

gestation through their mothers


or work

or work

or work
home

being involuntarily exposed to SHS


Table 2.10b Exposure to SHS and stomach cancer - Case-control studies

at work (OR=1.3; 95% CI=1.0-1.8)


or to all sources of SHS combined
assessment
Exposure

(OR=1.3; 95% CI=1.0-1.7). However,


risk of other histological types was
reduced in persons whose mother
smoked until pregnancy (OR=0.7;
95% CI=0.5-1.0) and who were
Characteristics

exposed during the first year of life


of controls

(OR=0.7; 95% CI=0.5-1.0). However,


these findings should be considered
in the context of the large number
of exposure groups and histological
Characteristics

types and the related risk for type I


of cases

error.

Is there a safe level of exposure


to SHS?
location, period

Studies of the relation between


Mao et al., 2002
Reference,

level of exposure to SHS and risk of


1994-1997

disease have not shown evidence


Canada

of a level below which the excess


risk is zero. That is, there are

56
Health effects of exposure to secondhand smoke (SHS)

no empirical data to support the been estimated for a number of among nonsmokers in 25 European
concept of a safe (harm-free) level populations. Making such estimations countries in 2002. The estimates
of exposure to SHS. This is not the requires assumptions about exposure are made with the assumptions of
same, of course, as demonstrating patterns and the risks of SHS-related causal associations of SHS exposure
that there is no threshold (other diseases applicable to particular with stroke and chronic respiratory
than zero exposure). However, the populations. While consequently disease, in addition to lung cancer
epidemiological findings need to be subject to uncertainty, the available and ischemic heart disease. The
considered alongside what is known estimates document that SHS has total burden is over 19 000 premature
about the toxicology of SHS and the substantial, while avoidable, public deaths annually.
likely biologic mechanisms of action, health impact. For example, estimates Methods for estimating the burden
which are referred to earlier in this made by the State of California for of disease attributable to SHS (and
chapter. It was on this basis that the both the state and for the entire USA other environmental exposures) at
2006 US Surgeon General’s report (see Table ES-2 from the California national and local levels have been
concluded “the scientific evidence EPA report), document thousands of reviewed recently by WHO (Prüss-
indicates that there is no risk-free premature deaths from cancer and Üstün & Corvalán, 2006). The burden
level of exposure to secondhand ischemic heart disease, as well as of disease associated with SHS
smoke” (U.S. Department of Health over 400 deaths attributable to SIDS exposure varies from population-to-
and Human Services, 2006). The each year in the USA (Table 2.11). population with the profile of exposure
Working Group agrees with this The morbidity burden for children is and the underlying rates of disease.
assessment. high (Table 2.11). For adults, the burden of attributable
Estimates made for Europe disease is strongly dependent on the
Burden of disease with a similar approach led to the rate of coronary heart disease, which
same conclusion on the public is a major contributor to mortality
Because of widespread exposure health significance of SHS exposure in many countries, not just in the
to SHS and the numerous adverse (Smoke Free Partnership, 2006). The wealthiest parts of the world.
consequences of exposure, the report, Lifting the Smokescreen: 10
impact on the health of children and Reasons for a Smokefree Europe,
adults is substantial. The burden provides estimates of the numbers
of disease attributable to SHS has of deaths attributable to SHS

Table 2.11 Contribution of SHS to the burden of disease in the United States - examples of health outcomes
attributable to SHS

Outcome Annual excess number due to SHS

Children born weighing <2500 g 24 500

Pre-term deliveries 71 900

Episodes of childhood asthma 202 300

Doctor visits for childhood otitis media 790 000

Deaths due to Sudden Infant Death Syndrome 430

Deaths due to Ischemic Heart Disease 46 000 (22 700 – 69 500)

Lung cancer deaths 3400

Adapted from California Environmental Protection Agency: Air Resources Board (2005)

57
IARC Handbooks of Cancer Prevention

Summary

This chapter describes the findings that SHS exposure contributes to the of causal associations. They have
of review groups that have conducted causation of cancer, cardiovascular also considered and rejected
comprehensive assessments of disease, and respiratory conditions. explanations other than causation
the health effects of exposure to The Working Group found a for the associations observed in the
SHS. Over the four decades that high degree of convergence of the epidemiological studies. Particular
research findings on SHS and research findings. In fact, since 1986, attention has been given to
health have been reported, stronger an increasing number of reports confounding by other risk factors
conclusions of reviewing groups have added to an ever growing list and to exposure misclassification,
have progressively motivated the of causal effects of SHS exposure. both of active smoking status and of
development of protective policies. These reports have given exhaustive exposure to SHS.
The rationale for such policies is consideration to the epidemiological
solidly grounded in the conclusions findings and the wide range of
of a number of authoritative groups: research supporting the plausibility

58