Cancer

Epidemiology,
Biomarkers
& Prevention

Letter to the Editor

Urinary Bladder Cancer Risk Factors in EgyptLetter

ning
Thomas Behrens, Beate Pesch, and Thomas Bru

In the journal, Zheng and colleagues reported a weaker

bladder cancer risk for active than passive smoking based
on results from a casecontrol study in Egypt (1). In total,
1,886 pathologically confirmed cases with urothelial cell
or squamous cell carcinoma (SCC) of the bladder and
2,716 controls were included. Control subjects were selected using random sampling of households and health units
via family health records. Participation rates were higher
for controls than cases. Unconditional logistic regression
analyses were calculated adjusting for governorate of
residence, urban/rural residence, age, education, urinary
tract infections other than schistosomiasis, and menopause status (among women). Other risk factors, for
example, occupational exposure to aromatic amines, were
not assessed.
Besides infection with Schistosoma haematobium, smoking was confirmed as the most important risk factor for
bladder cancer. However, rather implausibly, exposure to
environmental tobacco smoke was associated with a
higher risk as compared with heavy active smoking.
Furthermore, the risk for urothelial cell bladder cancer
only slightly increased with increasing number of packyears, SCC bladder cancer risk was only marginally elevated among cigarette smokers, and no dose-dependent
risk increase for SCC bladder cancer was seen with

Authors' Afliation: Institute for Prevention and Occupational Medicine,

German Social Accident Insurance, Institute of Ruhr-University Bochum
(IPA), Bochum, Germany
Corresponding Author: Thomas Behrens, Institute for Prevention and
Occupational Medicine, German Social Accident Insurance, Ruhr-Univerrkle-de-la-Camp-Platz 1, Bochum 44789, Germany.
sity Bochum (IPA), Bu
Phone: 49-234-3024794; Fax: 49-234-3024505; E-mail:
behrens@ipa-dguv.de
doi: 10.1158/1055-9965.EPI-12-0003
2012 American Association for Cancer Research.

increasing number of pack-years. These findings are in

contrast to a pooled analysis of 9 European casecontrol
studies (2) and a recent U.S. cohort study (3), which
showed a clear doseresponse relation for number of
pack-years and SCC risk. However, the authors fail to
acknowledge and discuss these findings. Also, bladder
cancers were not histopathologically graded according to
their invasiveness, although a recent casecontrol study
clearly showed that tobacco-related risks are higher for
more invasive tumors (4).
The studys results raise numerous questions about the
design and potential sources of bias, including the heterogeneous control sampling techniques, or the surprisingly high response among controls. Recruitment and
collection of smoking information are not sufficiently
explained. How reliable was self-reported active and
passive smoking behavior by disease status, education,
or other factors? Simultaneous adjustment for place of
residence and rural/urban residence may result in overadjustment with dilution of effect estimates toward unity.
Furthermore, detailed information on the pathologic classification of the cases would be helpful to explain why 757
cases, which were not included in the present analysis,
still await pathologic confirmation. As observational studies are prone to bias, we need to carefully reflect potential
limitations when interpreting a studys major findings
that are in conflict with the literature.
Disclosure of Potential Conicts of Interest
No potential conflicts of interests were disclosed.

Authors' Contribution
Writing, review, and/or revision of the manuscript: T. Behrens, B. Pesch,
T. Br
uning.
Received January 2, 2012; accepted January 6, 2012; published
OnlineFirst February 10, 2012.

References
1. Zheng YL, Amr S, Saleh D, Dash C, Ezzat S, Mikhail NN, et al. Urinary
bladder cancer risk factors in Egypt: a multi-center case-control study.
Cancer Epidemiol Biomarkers Prev 2012;21:53746.
lez CA, Hours M,
2. Fortuny J, Kogevinas M, Chang-Claude J, Gonza
ckel KH, et al. Tobacco, occupation and non-transitional-cell carciJo
noma of the bladder: an international case-control study. Int J Cancer
1999;80:446.

www.aacrjournals.org

3. Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC.

Association between smoking and risk of bladder cancer among men
and women. JAMA 2011;306:73745.
4. Jiang X, Castelao JE, Yuan JM, Stern MC, Conti DV, Cortessis VK, et al.
Cigarette smoking and subtypes of bladder cancer. Int J Cancer
2012;130:896901.

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