García-Closas M et al. (2005) NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet 366: 649–659

A study recently published in The Lancet has revealed strong associations between two carcinogen-detoxifying genes—NAT2 and GSTM1—and the risk of bladder cancer. The research by García-Closas and co-workers investigated polymorphisms in several NAT and GST genes in participants in the Spanish Bladder Cancer Study.

DNA samples were provided by patients (n = 1,150) diagnosed with carcinoma of the urinary bladder, and control individuals (n = 1,149) matched for age, sex, and geographical region who had been admitted to participating hospitals for unrelated conditions. All patients were white and were predominantly male.

The risk of bladder cancer was 40% higher in patients with NAT2 slow-acetylator genotypes than in intermediate-acetylator or rapid-acetylator genotypes (P = 0.0002). Regression analysis also revealed a stronger association between smoking and risk of bladder cancer among NAT2 slow-acetylator genotypes, than among either intermediate-acetylator or rapid-acetylator genotypes (P = 0.008). Individuals with the GSTM1 null genotype also had a significantly increased risk of bladder cancer compared with those who had one or two copies of the gene (P <0.0001), although the relative risk was not affected by smoking status. No significant interactions were found for the other genetic polymorphisms investigated. The authors also used the data from this study to update several previously published meta-analyses, which supported the convincing associations between bladder cancer and both NAT2 slow-acetylation and GSTM1 deletion.