American Journal of Epidemiology Vol. 172, No.

12
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October 15, 2010

Original Contribution

Alcohol Consumption Over Time and Risk of Lymphoid Malignancies in the

California Teachers Study Cohort

Ellen T. Chang*, Christina A. Clarke, Alison J. Canchola, Yani Lu, Sophia S. Wang, Giske Ursin,
Dee W. West, Leslie Bernstein, and Pamela L. Horn-Ross
* Correspondence to Dr. Ellen T. Chang, Cancer Prevention Institute of California, 2201 Walnut Avenue, Suite 300, Fremont, CA
94538 (e-mail: ellen@cpic.org).

Initially submitted April 30, 2010; accepted for publication August 12, 2010.

Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin
lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former
drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of
alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California
Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were
diagnosed with multiple myeloma between 1995–1996 and December 31, 2007. Incidence rate ratios and 95%
confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL
combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or
liquor at ages 18–22 years, at ages 30–35 years, or during the year before baseline. NHL subtypes were in-
consistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at
elevated risk of overall B-cell NHL (rate ratio ¼ 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma
(rate ratio ¼ 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the
importance of classifying both current and past alcohol consumption and suggests that factors related to quitting
drinking, rather than alcohol itself, may increase B-cell NHL risk.

alcohol drinking; cohort studies; lymphoma, non-Hodgkin; multiple myeloma

Abbreviations: CI, confidence interval; CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; DLBCL, diffuse large
B-cell lymphoma; ICDO-3, International Classification of Diseases for Oncology, Third Edition; NHL, non-Hodgkin lymphoma; RR,
rate ratio.

Alcohol intake can modulate immune function (1, 2),
an important etiologic factor for lymphoid malignancies
(3–6). A pooled analysis of 9 case-control studies of non-
Hodgkin lymphoma (NHL) revealed that ever drinkers,
compared with never drinkers, had a 17% lower risk of
NHL, a finding potentially explained by a beneficial effect
of moderate alcohol consumption on immune function
(7). However, the results showed no evident dose-
response relations, possibly arguing against a biologic
basis for the inverse association. Results of case-control
studies of multiple myeloma, another B-cell malignancy
that may be etiologically related to immune perturbation
(8), have been variable, with some investigators finding no
association (9–12) and others reporting at least a marginal
inverse association (13–15). In 6 large prospective cohort
studies of alcohol and NHL, investigators found that mod-
erate alcohol intake was associated with a 41% reduction
in risk among Iowa women (16), while heavier alcohol
intake was associated with risk reductions of 33% among
United Kingdom women (17), 23% among retired US
men and women (18), and 40% among Japanese men
(19). However, alcohol intake was not associated with
NHL risk among Finnish male smokers (20) or US men
and women in a cancer screening trial (21) or with mul-
tiple myeloma risk in the Finnish and Japanese cohorts
(19, 20).

1373 Am J Epidemiol 2010;172:1373–1383

1374 Chang et al.
Recent media reports have highlighted findings of a pos-
sible protective effect of alcohol against lymphoma devel-
opment (7), contributing to public confusion over whether
alcohol is good or bad for general health. Thus, it is impor-
tant from a public health standpoint to clarify whether mod-
ifying alcohol consumption can reduce lymphoma risk. In
support of the premise that alcohol use is not protective
against lymphoma, it has been documented for decades that
a sizeable proportion of persons with preclinical lymphoma
experience acute, intense pain and/or intolerance upon in-
gestion of alcohol, usually leading to voluntary cessation of
alcohol consumption (22, 23). In addition, several chronic
diseases are associated with increased risk of lymphoid ma-
lignancies (24–26) and can also influence lifestyle choices,
including cessation of alcohol use. Therefore, failure to dis-
tinguish former drinkers from never drinkers could result in
an artifactual association between current alcohol consump-
tion and reduced lymphoma risk.
Because most previous studies have not addressed this
issue, we examined the association between alcohol intake
and risk of lymphoid malignancies in a large, prospective
cohort study, the California Teachers Study. In the Califor-
nia Teachers Study, we have collected detailed data on al-
cohol consumption at and before cohort entry, along with
data from more than a decade of follow-up.
MATERIALS AND METHODS
Study population
The California Teachers Study cohort includes 133,479
active and retired female public school teachers and admin-
istrators who completed a mailed, self-administered baseline
questionnaire in 1995–1996 evaluating a range of factors re-
lated to cancer risk and women’s health (27). For this analy-
sis, we sequentially excluded participants who, at baseline,
were not residents of California (n ¼ 8,867); had an unknown
prior history of cancer (n ¼ 663); consented to participate
only in analyses of breast cancer (n ¼ 18); had previously
been diagnosed with NHL, multiple myeloma, Hodgkin lym-
phoma, or leukemia (n ¼ 536); were aged 85 years or older
(n ¼ 2,179) or under age 30 years (n ¼ 5,373); or had invalid
or inconsistent data on alcohol intake (n ¼ 10,664) or missing
data on alcohol intake during the year before baseline (n ¼
2,458). Of the 102,721 remaining women included in this
analysis, 496 were diagnosed with B-cell NHL (including
chronic lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL); International Classification of Diseases for On-
cology, Third Edition (ICDO-3), morphology codes 9591,
9670–9699, 9727, 9823, 9832, 9835, 9836, and 9940) and
101 were diagnosed with multiple myeloma (including plas-
macytoma; ICDO-3 codes 9731–9734) (28) after joining the
cohort, through December 31, 2007. The 3 most common B-
cell NHL histologic subtypes were diffuse large B-cell lym-
phoma (DLBCL) (n ¼ 139; ICDO-3 codes 9678–9680 and
9684), follicular lymphoma (n ¼ 111; ICDO-3 codes 9690,
9691, 9695, and 9698), and CLL/SLL (n ¼ 111; ICDO-3
codes 9670 and 9823).
Human subjects research in this study was approved by the
institutional review boards at all participating institutions.
Alcohol assessment
On the baseline questionnaire, participants reported aver-
age weekly consumption (0,
3, 4–10, 11–17, 18–24, or
25 drinks per week) of beer, wine/champagne, and cock-
tails/liquor during the year before study entry, at ages 30–35
years, and at ages 18–22 years. They also reported how
many days per week they usually drank each beverage. A
typical drink was defined as 1 bottle, can, or glass of beer; 1
glass of wine or champagne or 1 wine cooler; or 1 cocktail,
shot, or mixed drink of liquor. A single drink of beer, wine,
or liquor was assumed to contain 13.2 g, 13.3 g, or 20.0 g of
alcohol, respectively, for women aged <30 years; 13.2 g,
11.1 g, or 15.0 g of alcohol, respectively, for women aged
30–59 years; and 13.2 g, 9.2 g, or 15.0 g of alcohol, re-
spectively, for women aged 60 years (29, 30). On the basis
of these standards, we calculated daily intake of alcohol in
grams from each type of drink during each time period, and
we classified intake using cutoffs approximately equivalent
to half or full drinks of wine (the most commonly consumed
alcoholic beverage in the cohort) per day. Alcohol intake as
reported in our food frequency questionnaire was reproduc-
ible (q ¼ 0.87) and valid (q ¼ 0.74) in comparison with
multiple 24-hour recalls in a subset of cohort members (31).
For analyses of alcohol intake during the year before
baseline, we classified women as former drinkers if they
reported no baseline alcohol consumption but did report
having consumed alcohol at ages 18–22 years and/or 30–
35 years. Women who reported not having consumed alco-
hol during all 3 time periods were classified as consistent
nondrinkers. For analyses of alcohol intake at ages 30–35
years, we classified women as former drinkers if they re-
ported no alcohol consumption at that age but did report
having consumed alcohol at ages 18–22 years. Women
who reported not having consumed alcohol at ages 18–22
or 30–35 years but who did consume alcohol during the year
before baseline were classified separately. For analyses of
beer, wine, and liquor intake, we classified women as cur-
rent, former, or consistent nondrinkers of that specific type
of alcoholic beverage, using the same logic.
Follow-up
Participants were followed from the date of completion of
the baseline questionnaire to the date of a first diagnosis
with a hematopoietic malignancy, relocation out of Califor-
nia, death, or December 31, 2007, whichever occurred ear-
liest. Participants diagnosed with T-cell NHL (n ¼ 43), NHL
of unknown histologic type (n ¼ 22), Hodgkin lymphoma
(n ¼ 33), or leukemia (n ¼ 116; other ICDO-3 morphology
codes between 9590 and 9989) during follow-up were cen-
sored at the date of diagnosis. Information on incident can-
cers was obtained through annual linkage of cohort
members to the population-based California Cancer Regis-
try, which is over 99% complete. Linkages with the Cali-
fornia state mortality file and the national Social Security
Administration death master file were used to ascertain date
and cause of death. Address changes were obtained through
record linkages with multiple sources, including the
National Change of Address database, change-of-address
Am J Epidemiol 2010;172:1373–1383
 Alcohol and Lymphoid Malignancies 1375

Table 1. Baseline Demographic Characteristics of Cohort pesticide/herbicide/insecticide use at various ages, urban/
Members Eligible for Analysis of Alcohol Consumption and Risk of rural residence, and neighborhood-level socioeconomic sta-
Lymphoid Malignancies (n ¼ 102,721), California Teachers Study, tus. None of these factors altered the associations with
1995–1996 alcohol intake by more than 10% after multivariable adjust-
Characteristic No. % ment; therefore, none were included in the final regression
models. In models of associations with specific alcoholic
Age, years
beverage types, all estimates were mutually adjusted for
30–39 14,654 14 beer, wine, and liquor intake.
40–49 29,101 28 The proportional hazards assumption was not violated by
50–59 26,871 26 any of the main categories of alcohol consumption, based on
60–69 18,043 18 significance tests of interactions between the exposure and
70–79 11,341 11
the time scale and visual assessment of the time-to-event
curves. All tests of statistical significance were 2-sided.
80–84 2,711 3
Analyses were performed using SAS, version 9.1.3 (SAS
Race/ethnicity Institute, Inc., Cary, North Carolina).
White, non-Hispanic 89,576 87
Black, non-Hispanic 2,672 3
Hispanic/Latina 3,997 4 RESULTS
Asian or Pacific Islander 3,745 4
Table 1 shows the distribution of selected baseline char-
Other or mixed 1,968 2 acteristics in the study population. As shown in Table 2,
Missing data 763 1 which presents the associations with alcohol intake in the
Residential setting year before baseline, we found a statistically significant
Rural area/small town 18,199 18 positive association between former alcohol consumption,
City 18,520 18
compared with consistent nondrinking, and risk of overall
B-cell NHL. We observed no association of overall B-cell
Metropolitan suburban area 54,881 53
NHL risk with any level of alcohol consumption in the year
Metropolitan urban area 9,835 10 before baseline. Likewise, baseline and former beer, wine,
Missing data 1,286 1 and liquor consumption were not statistically significantly
Neighborhood socioeconomic associated with overall B-cell NHL risk, nor was frequency
status (state population quartile) of consuming each type of beverage (1–4 days/week or
1 (lowest) 4,357 4 5–7 days/week vs. consistent nondrinking; latter data not
2 17,616 17 shown).
3 33,113 32
For the sake of comparison with results from previous
studies, when we combined former drinkers with consistent
4 (highest) 46,311 45
nondrinkers as the reference group, the rate ratios for associ-
Missing data 1,324 1 ations with alcohol intake in the year before baseline de-
creased (for baseline total alcohol intake of <5 g/day vs.
never/former drinking, rate ratio (RR) ¼ 1.00 (95% confi-
dence interval (CI): 0.79, 1.28); for 5–<10 g/day, RR ¼ 0.84
forms from annual mailed newsletters, and proactive notifi- (95% CI: 0.65, 1.09); for 10–<20 g/day, RR ¼ 0.86 (95% CI:
cations by participants. 0.66, 1.11); and for 20 g/day, RR ¼ 1.00 (95% CI: 0.73,
Statistical analysis 1.39)). By contrast, when we combined former drinkers with
persons who consumed alcohol during the year before base-
Associations between alcohol intake and risk of lymphoid line, the rate ratio for any drinking versus consistent non-
malignancies were estimated using Cox proportional haz- drinking was increased (RR ¼ 1.12, 95% CI: 0.90, 1.40).
ards regression, with age (in days) as the time scale and data In analyses of B-cell NHL subtypes, former consumption
stratified by age (in years) at baseline to adjust for calendar- of total alcohol or wine at baseline was associated with in-
year effects. Incidence rate ratios were estimated as hazard creased risk of follicular lymphoma (Table 2). Average in-
ratios and 95% confidence intervals comparing former or take of <10 g/day (but not 10 g/day) of alcohol was
current alcohol drinkers with consistent nondrinkers (of to- marginally associated with reduced risk of DLBCL,
tal alcohol or a specific alcoholic beverage type). On the whereas any alcohol intake during the year before baseline
basis of prior knowledge and independent associations with was associated with increased risk of CLL/SLL. We ob-
risk of overall B-cell NHL, NHL subtypes, or multiple my- served no apparent associations between alcohol consump-
eloma, we assessed a broad range of potential confounders, tion in the year before baseline and risk of multiple
including race/ethnicity, birthplace, total energy intake, in- myeloma.
take of fruits and vegetables, body mass index, sunburn As Table 3 shows, we observed no association of total
history, family history of hematopoietic cancer, personal alcohol consumption at ages 18–22 years or 30–35 years
history of melanoma or other skin cancer, number of older with risk of overall B-cell NHL, DLBCL, follicular lym-
siblings, age at menarche, menopausal hormone therapy, phoma, or multiple myeloma, whereas consumption of any

Am J Epidemiol 2010;172:1373–1383
1376 Chang et al.

Table 2. Incidence Rate Ratios for the Associations of Alcohol Intake During the Year Before
Baseline With Risk of B-Cell Non-Hodgkin Lymphoma, Non-Hodgkin Lymphoma Subtypes, and
Multiple Myeloma, California Teachers Study, 1995–2007

95% Confidence
Alcohol Intake No. of Cases Rate Ratioa
Interval

Overall B-Cell Non-Hodgkin Lymphoma

Total alcohol
Consistent nondrinker 100 1.00 Reference
Former alcohol drinker 76 1.46 1.08, 1.97
Current drinker, g/day
0.1–<5 101 1.16 0.88, 1.54
5–<10 83 0.98 0.73, 1.31
10–<20 85 0.99 0.74, 1.33
20 46 1.16 0.82, 1.65
Beer
Consistent beer nondrinker 276 1.00 Reference
Former beer drinker 91 1.20 0.92, 1.55
Any current beer consumption 97 0.97 0.75, 1.25
Wine
Consistent wine nondrinker 130 1.00 Reference
Former wine drinker 68 1.26 0.90, 1.76
Current wine drinker, g/day
0.1–<5 196 1.06 0.82, 1.38
5 70 0.82 0.59, 1.13
Liquor
Consistent liquor nondrinker 186 1.00 Reference
Former liquor drinker 125 1.09 0.84, 1.41
Current liquor drinker, g/day
0.1–<5 118 1.09 0.83, 1.43
5 35 1.07 0.73, 1.57
Diffuse Large B-Cell Lymphoma
Total alcohol
Consistent nondrinker 37 1.00 Reference
Former alcohol drinker 21 1.11 0.65, 1.90
Current drinker, g/day
0.1–<10 42 0.67 0.43, 1.04
10 38 0.84 0.53, 1.33
Beer
Consistent beer nondrinker 91 1.00 Reference
Former beer drinker 20 0.88 0.52, 1.49
Any current beer consumption 18 0.60 0.35, 1.04
Wine
Consistent wine nondrinker 50 1.00 Reference
Former wine drinker 14 0.74 0.38, 1.43
Any current wine consumption 65 0.74 0.47, 1.15
Liquor
Consistent liquor nondrinker 61 1.00 Reference
Former liquor drinker 32 1.18 0.71, 1.94
Any current liquor consumption 36 1.06 0.65, 1.73
Table continues

Am J Epidemiol 2010;172:1373–1383
 Alcohol and Lymphoid Malignancies 1377

Table 2. Continued

95% Confidence
Alcohol Intake No. of Cases Rate Ratioa
Interval

Follicular Lymphoma
Total alcohol
Consistent nondrinker 22 1.00 Reference
Former alcohol drinker 22 1.81 1.00, 3.28
Current drinker, g/day
0.1–<10 40 1.03 0.61, 1.73
10 26 0.91 0.51, 1.61
Beer
Consistent beer nondrinker 58 1.00 Reference
Former beer drinker 25 1.45 0.86, 2.43
Any current beer consumption 25 1.25 0.74, 2.11
Wine
Consistent wine nondrinker 26 1.00 Reference
Former wine drinker 22 2.08 1.09, 3.99
Any current wine consumption 60 1.21 0.71, 2.07
Liquor
Consistent liquor nondrinker 47 1.00 Reference
Former liquor drinker 31 0.82 0.49, 1.37
Any current liquor consumption 30 0.71 0.42, 1.20
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Total alcohol
Consistent nondrinker 14 1.00 Reference
Former alcohol drinker 12 1.76 0.81, 3.82
Current drinker, g/day
0.1–<10 50 2.14 1.18, 3.88
10 33 1.93 1.03, 3.63
Beer
Consistent beer nondrinker 58 1.00 Reference
Former beer drinker 22 1.30 0.77, 2.19
Any current beer consumption 22 0.83 0.49, 1.41
Wine
Consistent wine nondrinker 20 1.00 Reference
Former wine drinker 11 1.23 0.54, 2.79
Any current wine consumption 71 1.45 0.81, 2.60
Liquor
Consistent liquor nondrinker 30 1.00 Reference
Former liquor drinker 27 1.31 0.72, 2.37
Any current liquor consumption 45 1.64 0.96, 2.82
Multiple Myeloma
Total alcohol
Consistent nondrinker 28 1.00 Reference
Former alcohol drinker 14 1.01 0.53, 1.93
Current drinker, g/day
0.1–<10 31 0.65 0.39, 1.09
10 27 0.80 0.47, 1.36
Table continues

Am J Epidemiol 2010;172:1373–1383
1378 Chang et al.
Table 2. Continued
Alcohol Intake
Beer
Consistent beer nondrinker
Former beer drinker
Any current beer consumption
Wine
Consistent wine nondrinker
Former wine drinker
Any current wine consumption
Liquor
Consistent liquor nondrinker
Former liquor drinker
Any current liquor consumption
a
Rate ratios were adjusted for age (as the time scale) and calendar-year effects. In models for
specific alcohol types, results were mutually adjusted for the other types of alcohol.
alcohol during either age interval was associated with in-
creased risk of CLL/SLL. When we examined intake of
specific alcoholic beverages at ages 18–22 years and 30–
35 years, we did not detect any consistent inverse or pos-
itive associations with risk of any lymphoid malignancies
(see Web Table 1, which is posted on the Journal’s Web
site (http://aje.oxfordjournals.org/)). The results for alco-
hol intake at ages 30–35 years were unchanged when the
analysis was limited to women aged 40 years at baseline,
thereby ensuring that reported intake was at least 5 years in
the past (data not shown). When we examined changes in
alcohol intake across the time periods assessed, including
total alcohol intake of 20 g/day in all 3 periods (1% of the
cohort; n ¼ 5 cases), we observed no meaningful patterns
of association (data not shown).
To assess whether the positive associations of former
drinking during the year before baseline with risks of
overall B-cell NHL and follicular lymphoma were due
to prodromal symptoms, we performed a secondary anal-
ysis after excluding the first 3 years of follow-up (n ¼
381 B-cell NHL cases, n ¼ 102 DLBCL cases, n ¼ 85
follicular lymphoma cases, n ¼ 82 CLL/SLL cases, and
n ¼ 78 multiple myeloma cases). The results were not
appreciably affected, with the exception that former al-
cohol consumption was associated with increased risk of
CLL/SLL (RR ¼ 2.85, 95% CI: 1.08, 7.51) as well as
overall B-cell NHL and follicular lymphoma (other data
not shown).
To examine associations with recent alcohol drinking, we
performed a secondary analysis of baseline alcohol con-
sumption limited to the first 5 years of follow-up (through
December 31, 2000; n ¼ 201 B-cell NHL cases). In this
analysis, the relation between recent alcohol consumption
and overall B-cell NHL risk showed evidence suggestive
of a U-shaped curve. The rate ratios for B-cell NHL associ-
ated with total alcohol intake, versus consistent nondrinking,
were 1.19 (95% CI: 0.79, 1.79) for <5 g/day, 0.67 (95% CI:
0.41, 1.09) for 5–<10 g/day, 0.77 (95% CI: 0.48, 1.24) for
10–<20 g/day, and 1.38 (95% CI: 0.84, 2.27) for 20 g/day.
95% Confidence
No. of Cases Rate Ratioa
Interval
60 1.00 Reference
15 1.04 0.56, 1.94
14 0.85 0.45, 1.61
34 1.00 Reference
15 1.31 0.64, 2.65
40 0.65 0.37, 1.13
43 1.00 Reference
21 0.91 0.49, 1.68
25 1.01 0.56, 1.81
Finally, to examine whether associations with alcohol
consumption changed after exclusion of cases with rapidly
fatal disease, who are less likely to be included in case-
control studies, we performed a secondary analysis ex-
cluding B-cell NHL cases who died within 18 months of
diagnosis (n ¼ 88 cases). The results did not differ appre-
ciably from those in the primary analysis (data not shown).
DISCUSSION
In this large, prospective cohort study of California
women, we found little evidence that alcohol consumption
during various time periods in adulthood is associated with
risk of overall B-cell NHL or multiple myeloma, although
we may have lacked sufficient statistical power to detect
associations. We detected a weak inverse association of
moderate baseline alcohol intake with risk of DLBCL, but
the association was not consistent across different types of
alcoholic beverages, nor did risk decline with increasing
total alcohol intake, suggesting that the observed association
was not due to an effect of alcohol itself. Conversely, we
found positive associations of alcohol intake at all assessed
time points with risk of CLL/SLL, although most of these
associations lacked evidence of a dose-response trend. Thus,
the observed associations with risk of DLBCL and CLL/
SLL may have been due to chance or confounding. Alter-
natively, these associations may reflect true biologic hetero-
geneity between NHL subtypes and could perhaps point to
an effect of alcohol on B-cell differentiation.
Most notably, we observed positive associations between
former intake of alcohol in the year before baseline and risk
of overall B-cell NHL, follicular lymphoma, and possibly
CLL/SLL. This result was not explained by the wide array
of confounders examined and may point to an etiologic role
of other factors, such as illness or efforts to improve general
health, that lead to cessation of alcohol use. The persistence
of the positive association with former drinking after we
excluded diagnoses made within 3 years of baseline indi-
cates that such factors are unlikely to be alcohol pain/
Am J Epidemiol 2010;172:1373–1383

intolerance or other preclinical symptoms of lymphoma or
that such symptoms occur more than 3 years before diagno-
sis. This general premise is consistent with our observation
that recent moderate alcohol consumption (within the past 5
years) was suggestively associated with decreased risk of
overall B-cell NHL, indicating that current alcohol con-
sumption may be a surrogate for better current health.
The limited evidence of an inverse association with
DLBCL risk in our study accords with the inverse associ-
ation detected in an InterLymph pooled analysis of 9 NHL
case-control studies (7) and several other studies (10, 12,
32–34) and in 4 of 6 prospective cohort studies of NHL
(16–19). A number of biologically plausible mechanisms
could underlie such a protective effect. Whereas heavy
alcohol intake has been shown to have immunosuppressive
effects that result in increased susceptibility to infections
and impaired host response to injury (1), light or moderate
alcohol consumption can have a beneficial attenuating ef-
fect on proinflammatory cytokines and chemokines
(35, 36) that may otherwise promote lymphomagenesis
(37). Alcohol can also increase insulin sensitivity (38),
which may in turn decrease NHL risk (39). Antioxidants
such as resveratrol in wine and flavonoids in beer may have
additional anticarcinogenic effects (40, 41), and alcoholics
have been found to have better DNA repair capacity than
nonalcoholics (42).
However, our overall finding of no association of alco-
hol consumption with risk of B-cell NHL or multiple
myeloma is more consistent with the results of previous
case-control studies (9, 11, 43–47) and 2 prospective
cohort studies (20, 21) that similarly detected no associa-
tion. Some of the heterogeneity among previous studies
may be due in part to the substantial potential for recall
and selection biases in retrospective case-control studies.
Given that alcohol consumption has variable connotations
of social and cultural desirability (48) and is well known
to affect health, cases may report alcohol intake differ-
ently from controls, resulting in recall bias. In addition,
early symptoms or the diagnosis itself may cause patients
to stop drinking alcohol, leading to a false inverse associ-
ation between alcohol consumption and disease risk at the
time of the study interview. Finally, if alcohol consump-
tion is associated not with NHL or multiple myeloma risk
but with more severe or fatal disease, then case-control
studies, in which deceased patients are usually excluded
and those with debilitating disease often do not partici-
pate, may again detect a spurious inverse association
with alcohol consumption. Therefore, prospective cohort
studies generally have higher validity for assessing the
etiologic role of alcohol intake.
Nonetheless, in both retrospective and prospective stud-
ies, it is important to collect information on not only cur-
rent alcohol intake but also past alcohol intake to
distinguish among current, former, and never drinkers.
Given that poor health is a major reason for reducing or
ceasing alcohol consumption (30), former drinkers may
have higher disease risk than never drinkers or current
drinkers. Therefore, regardless of study design, combining
former drinkers with never drinkers may produce a spuri-
ous inverse association with current drinking, whereas
Am J Epidemiol 2010;172:1373–1383
Alcohol and Lymphoid Malignancies 1379
combining former drinkers with current drinkers may gen-
erate a false-positive association or obscure a true inverse
association. Indeed, in our study, when we combined never
drinkers with former drinkers as the reference group, the
association with current alcohol intake was decreased,
whereas combining former drinkers with current drinkers
inflated the association with ever drinking. Nearly all pre-
vious studies of alcohol and risk of lymphoid malignancies
combined former drinkers with either never drinkers or
current drinkers, and many investigators were unclear
about whether ‘‘alcohol consumption’’ referred to current
(excluding former) drinking or ever (including former)
drinking. A few studies included in the InterLymph anal-
ysis (7) classified former drinkers as a separate group and
found no association between former (versus never) drink-
ing and risk of NHL or its histologic subtypes. However,
none of the previous 5 prospective cohort studies of alco-
hol and risk of lymphoid malignancies analyzed former
alcohol intake separately.
Another potential source of misclassification in previ-
ous studies of alcohol and risk of lymphoid malignancies
is a failure to distinguish between never drinkers and oc-
casional drinkers, who can differ markedly in behaviors,
health status, and—particularly if abstinence is due to
religious or cultural reasons—genetic traits (30). Espe-
cially in European studies, true abstainers have often been
combined with infrequent drinkers (e.g., <1 drink
monthly or weekly) for comparison with frequent drinkers
(10, 12, 33, 47). Such variability in the definition of the
reference group for relative risk estimates may explain some
of the inconsistency in results among previous studies.
In the California Teachers Study, we prospectively col-
lected information on recent and past alcohol consumption,
and our questionnaire distinguished between women who
consumed low quantities of alcohol and those who did not
drink at all, enabling us to classify women according to both
past alcohol intake and true abstinence. This information
was necessary to reveal that risks of overall B-cell NHL
and follicular lymphoma differed between former drinkers
and never drinkers.
However, our study had some limitations. First, we did
not assess alcohol intake continuously throughout the par-
ticipant’s lifetime and therefore could not construct a de-
tailed history of alcohol consumption. Second, our analyses
were constrained by the limited number of incident cases,
which prevented us from examining numerous categories of
alcohol intake, drinking patterns over time, or associations
with less common lymphoma subtypes. Notably, 2 of the
previous prospective cohort studies that observed an inverse
association with alcohol consumption had substantially
more incident cases than we did (17, 18), giving them con-
siderably more statistical power to detect a true association.
Thus, the absence of an association with risk of overall
B-cell NHL, some NHL subtypes, and multiple myeloma
in our study may have been due to insufficient statistical
power. Third, we did not assess reasons for cessation
of alcohol consumption and therefore could not com-
pare women who quit drinking because of ill health with
those who quit for other reasons. Finally, we could not ex-
amine the effects of changes in alcohol consumption
1380 Chang et al.

Table 3. Incidence Rate Ratios for Associations of Age-Specific Total Alcohol Intake at Ages
18–22 Years and 30–35 Years With Risk of B-Cell Non-Hodgkin Lymphoma, Non-Hodgkin
Lymphoma Subtypes, and Multiple Myeloma, California Teachers Study, 1995–2007

95% Confidence
Age-Specific Alcohol Intake No. of Cases Rate Ratioa
Interval

Overall B-Cell Non-Hodgkin Lymphoma

Ages 18–22 years
Consistent nondrinker 100 1.00 Reference
No consumption at ages 18–22 years 145 1.08 0.84, 1.40
Consumption at ages 18–22 years, g/day
0.1–<5 43 1.04 0.72, 1.49
5–<10 103 1.14 0.86, 1.50
10–<20 44 1.16 0.81, 1.66
20 28 1.40 0.91, 2.14
Ages 30–35 years
Consistent nondrinker 100 1.00 Reference
Former drinker at ages 30–35 years 18 1.40 0.84, 2.33
No consumption at ages 26 0.97 0.63, 1.49
18–22 and 30–35 years
Consumption at ages 30–35 years, g/day
0.1–<5 91 1.09 0.82, 1.45
5–<10 89 1.03 0.77, 1.37
10–<20 108 1.30 0.98, 1.71
20 30 0.97 0.64, 1.46
Diffuse Large B-Cell Lymphoma
Ages 18–22 years
Consistent nondrinker 37 1.00 Reference
No consumption at ages 18–22 years 38 0.78 0.49, 1.23
Consumption at ages 18–22 years, g/day
0.1–<10 39 0.80 0.51, 1.26
10 15 0.69 0.37, 1.28
Ages 30–35 years
Consistent nondrinker 37 1.00 Reference
No consumption at ages 30–35 years 10 0.68 0.34, 1.37
Consumption at ages 30–35 years, g/day
0.1–<10 43 0.69 0.45, 1.08
10 39 0.95 0.60, 1.49
Follicular Lymphoma
Ages 18–22 years
Consistent nondrinker 22 1.00 Reference
No consumption at ages 18–22 years 32 1.09 0.63, 1.88
Consumption at ages 18–22 years, g/day
0.1–<10 34 1.12 0.65, 1.92
10 20 1.42 0.76, 2.63
Table continues

(including cessation or resumption of drinking) after base-
line, which may have influenced subsequent risk of B-cell
NHL or multiple myeloma.
Despite these limitations, ours is the first prospective
cohort study of lymphoid malignancies to examine alcohol
intake before baseline and to distinguish current drinkers
from former drinkers at baseline. Our results are strength-
ened by detailed covariate data and complete and valid
follow-up for incident cancer among California residents.
In summary, we found that alcohol consumption is not

Am J Epidemiol 2010;172:1373–1383
 Alcohol and Lymphoid Malignancies 1381

Table 3. Continued

95% Confidence
Age-Specific Alcohol Intake No. of Cases Rate Ratioa
Interval

Ages 30–35 years

Consistent nondrinker 22 1.00 Reference
No consumption at ages 30–35 years 10 1.13 0.53, 2.38
Consumption at ages 30–35 years, g/day
0.1–<10 47 1.21 0.73, 2.02
10 29 1.08 0.62, 1.90
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Ages 18–22 years
Consistent nondrinker 14 1.00 Reference
No consumption at ages 18–22 years 39 1.99 1.08, 3.68
Consumption at ages 18–22 years, g/day
0.1–<10 32 1.86 0.99, 3.51
10 16 2.36 1.14, 4.90
Ages 30–35 years
Consistent nondrinker 14 1.00 Reference
No consumption at ages 30–35 years 8 1.47 0.62, 3.51
Consumption at ages 30–35 years, g/day
0.1–<10 50 2.15 1.19, 3.91
10 29 1.89 0.99, 3.61
Multiple Myeloma
Ages 18–22 years
Consistent nondrinker 28 1.00 Reference
No consumption at ages 18–22 years 25 0.66 0.38, 1.13
Consumption at ages 18–22 years, g/day
0.1–<10 21 0.60 0.34, 1.06
10 13 0.90 0.46, 1.76
Ages 30–35 years
Consistent nondrinker 28 1.00 Reference
No consumption at ages 30–35 years 7 0.63 0.27, 1.44
Consumption at ages 30–35 years, g/day
0.1–<10 31 0.67 0.40, 1.11
10 21 0.70 0.39, 1.23
a
Rate ratios were adjusted for age (as the time scale) and calendar-year effects.

associated with risk of overall B-cell NHL or multiple ACKNOWLEDGMENTS

myeloma and that former drinkers may have higher risks
of follicular lymphoma and CLL/SLL, for reasons that
may be related to illness, lifestyle changes, or other factors
that prompt people to stop drinking prior to diagnosis.
Moreover, the relation of alcohol consumption with B-cell
NHL risk may vary by histologic subtype. Future studies
of the role of alcohol in the development of lymphoid
malignancies or any other health outcomes should account
for former drinking and changing drinking patterns over
time. Only with consistent attention to these distinctions
can future investigators determine whether alcohol truly
protects against lymphomagenesis or whether other fac-
tors explain the inverse associations detected in past
studies.
Author affiliations: Cancer Prevention Institute of Cali-
fornia (formerly the Northern California Cancer Center),
Fremont, California (Ellen T. Chang, Christina A. Clarke,
Alison J. Canchola, Dee W. West, Pamela L. Horn-Ross);
Division of Epidemiology, Department of Health Research
and Policy, School of Medicine, Stanford University, Stan-
ford, California (Ellen T. Chang, Christina A. Clarke, Dee
W. West, Pamela L. Horn-Ross); Division of Cancer Etiol-
ogy, Department of Population Sciences, City of Hope Na-
tional Medical Center, Duarte, California (Yani Lu, Sophia
S. Wang, Leslie Bernstein); and Division of Epidemiology,
Department of Preventive Medicine, Norris Comprehensive

Am J Epidemiol 2010;172:1373–1383
1382 Chang et al.
Cancer Center, Keck School of Medicine, University of
Southern California, Los Angeles, California (Giske Ursin).
This work was supported by the National Cancer Institute
(grants R03 CA135687, R01 CA77398, and K05 CA136967)
and the California Breast Cancer Research Fund (contract 97-
10500). The collection of cancer incidence data used in this
study was supported by the California Department of Health
Services as part of the statewide cancer reporting program
mandated by the California Health and Safety Code (section
103885); the National Cancer Institute’s Surveillance, Epide-
miology, and End Results Program (contract N01-PC-35136
with the Cancer Prevention Institute of California, contract
N01-PC-35139 with the University of Southern California,
and contract N02-PC-15105 with the Public Health Institute);
and the Centers for Disease Control and Prevention’s Na-
tional Program of Cancer Registries (agreement U55/
CCR921930-02 with the Public Health Institute).
The funding sources did not contribute to the design or
conduct of the study or to the writing or submission of the
manuscript. The ideas and opinions expressed herein are
those of the authors, and endorsement by the state of
California, the California Department of Health Services,
the National Cancer Institute, or the Centers for Disease
Control and Prevention or their contractors and subcontrac-
tors is not intended and should not be inferred.
Conflict of interest: none declared.
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