N-acetyltransferase 2 Phenotype, Occupation, and Bladder Cancer Risk: Results from the EPIC Cohort

Abstract

Background: AnassociationbetweenN-acetyltransferase2(NAT2)slowacetylationandbladdercancerhasbeen consistently observed in epidemiologic studies. However, evidence has been mainly derived from case-control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case-controlstudy nested in the European Prospective Investigation into Cancer and Nutrition.Methods: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative jobexposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood samples.Results: Occupational exposure to aromatic amines and PAH was associated with an increased bladder cancer risk [upper tertile of the distribution of the exposure score: OR ¼ 1.37; 95% confidence interval (CI), 1.02-1.84, and OR ¼ 1.50; 95% CI, 1.09-2.05, respectively]. NAT2 slow acetylation did not modify these risk estimates and was not itself associated with bladder cancer risk (OR ¼ 1.02; 95% CI, 0.81-1.29).Conclusions: These findings confirm established or suspected occupational risk factors but not the anticipated role of NAT2 slow acetylation in bladder cancer. No interaction was detected between NAT2 and any exposure of interest, including smoking.Impact: Genetic testing for NAT2 would be inappropriate in occupational settings. Cancer Epidemiol Biomarkers Prev; 22(11); 2055-65. Ó2013 AACR.

Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends

“…For example, slow acetylation of N-acetyltransferase 2, a key enzyme in aromatic amines metabolism, is considered to increase susceptibility to tobacco smoke, polycyclic aromatic hydrocarbons, or other occupational carcinogens [2]. However, results remain inconsistent [53] and further research is needed on the association between polymorphisms in the different carcinogen metabolising enzymes and bladder cancer risk. In our study, we observed disparities in the burden of bladder cancer between the White and Black populations of the US but these are more likely to reflect risk determinants linked to socio-economic disparities than population variations in genetic factors [54].…”

PharmGKB summary

“…[165]), others do not after adjusting for multiple factors [35, 166]. Recent GWAS meta-analyses reveal multiple risk loci, including NAT2 [167].…”

NAT2 and Bladder Cancer—Response

“…Golka and colleagues (1) critically refer to our observation that NAT2 genotype had no impact on bladder cancer risk (2). We were able to demonstrate in our case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) that occupational exposure to aromatic amines and polycyclic aromatic amines was associated with an increased bladder cancer risk.…”