Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

Polymorphisms in GSTT1, GSTM1, NAT1 and NAT2 genes and bladder cancer risk in men and women

Monica McGrath123*, Dominique Michaud12 and Immaculata De Vivo123

Author Affiliations

1 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, 02115, USA

2 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, Massachusetts, 02115, USA

3 Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, 02115, USA

For all author emails, please log on.

BMC Cancer 2006, 6:239  doi:10.1186/1471-2407-6-239

Published: 6 October 2006

Abstract

Background

Cigarette smoking is an established risk factor for bladder cancer. Epidemiological and biological data suggest that genetic polymorphisms in activating and detoxifying enzymes may play a role in determining an individual's susceptibility to bladder cancer in particular when in combination with specific environmental exposures such as cigarette smoking. N-acetyltransferase (NAT) enzymes, NAT1 and NAT2, are involved in the activation and detoxification of tobacco smoke constituents. Polymorphisms in these genes alter the ability of these enzymes to metabolize carcinogens, as certain allelic combinations result in a slow or rapid acetylation phenotype. Glutathione S-transferases (GSTs) also detoxify tobacco smoke constituents, and polymorphisms within the GSTM1 and GSTT1 genes can result in a complete lack of enzyme activity.

Methods

We assessed the association between common polymorphisms identified in the GSTM1, GSTT1, NAT1, and NAT2 genes and the risk of bladder cancer in two nested case-control studies within the Nurses' Health Study (n = 78 female cases, 234 female controls) and the Health Professionals' Follow-up Study (n = 139 male cases, 293 male controls). We also evaluated whether cigarette smoking modified the associations of the genotypes and bladder cancer risk in men and women.

Results

Overall, we observed no statistically significant associations between the polymorphisms and bladder cancer risk among men and women, although given our sample size, we had limited power to detect small to moderate effects. There was however the suggestion of an increased risk among female ever smokers with the NAT2 slow genotype and an increased risk in male never smokers with the GSTM1 null genotype.

Conclusion

In summary, these prospective results are consistent with previous literature supporting associations between bladder cancer and the NAT2 slow acetylation and the GSTM1 null genotypes.