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N-acetyltransferase 2 phenotype, occupation, and bladder cancer risk: results from the EPIC cohort
Beate Pesch1, Katarzyna Gawrych, Sylvia Rabstein
1Authors' Affiliations: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Institute of the Ruhr University, Bochum; German Research Center for Environmental Health, Neuherberg; German Cancer Research Center (DKFZ), Heidelberg; Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Nuthetal; Department of Urology, University Hospital Charité, Berlin, Germany; The National Institute for Public Health and the Environment, Bilthoven; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands; Danish Cancer Society Research Centre, Danish Cancer Society, Copenhagen; Department of Public Health, Institute of Epidemiology and Social Medicine, Aarhus, Denmark; INSERM, Centre for Research in Epidemiology and Population Health, Gustave Roussy Institute, Villejuif; Genetic Epidemiology Group; Nutritional Epidemiology Group, International Agency for Research on Cancer (IARC/WHO), Lyon, France;Harvard School of Public Health, Boston, Massachusetts; Academy of Athens; Hellenic Health Foundation, Greece; Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence; Epidemiology and Prevention Unit, National Cancer Institute (IRCCS), Milano; Cancer Registry and Histopathology Unit, "Civile - M.P. Arezzo" Hospital, ASP Ragusa; Department of Clinical and Experimental Medicine, Federico II University, Medical School, Naples; HuGeF Foundation, Torino, Italy; Public Health and Health Planning Directorate, Asturias; Department of Epidemiology, Catalan Institute of Oncology, Barcelona; Andalusian School of Public Health; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Granada; Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian; Department of Epidemiology, Murcia Regional Health Authority, Murcia; Navarra Public Health Institute, Consortium for Biomedical Rese
Background:
An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been 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-control study 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 job-exposure 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 = 1.37; 95% confidence interval (CI), 1.02-1.84, and OR = 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 = 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.
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