ABSTRACT: Gender, smoking, glutathione-S-transferase variants and bladder cancer incidence: a population-based study

Objective. Male gender, tobacco smoking and occupational exposure to arylamines and polycyclic aromatic hydrocarbons are the primary risk factors for bladder cancer. Emerging, and consistent data indicate that risk may be modified by polymorphisms in carcinogen metabolism genes, including those involving the glutathione-S- transferases. Recent work further suggests that susceptibility to the carcinogenic effects of tobacco on the bladder may differ among men and women. Method. We investigated the gender specific risk of bladder cancer associated with glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms in a population-based case-control study of 354 bladder cancer cases and 542 controls. Results. We found an increased risk of bladder cancer associated with GSTM1 null genotype among women (OR 1.7; 95% CI 1.0–3.0), but not men (OR 0.9; 95% CI 0.7–1.3). Among women, the GSTM1 null genotype was associated with an elevated bladder cancer risk only among smokers (OR 2.3; 95% CI 1.1–4.5 in ever smokers versus OR 0.9; 95% CI 0.3–2.5 in never smokers). There was no apparent association between bladder cancer and the GSTT1 null polymorphism in either men or women, and we did not detect evidence of any GSTT1–smoking or GSTT1–GSTM1 gene–gene interaction. Conclusion. Our data suggest that a subset of women may be particularly susceptible to tobacco-induced bladder cancer.