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N-acetyltransferase 2 Phenotype, Occupation, and Bladder Cancer Risk: Results from the EPIC Cohort
Published version of a preprint
Abstract
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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Metadata
- Authors
- Pesch, B., Gawrych, K., Rabstein, S., Weiss, T., Casjens, S., Rihs, H.-P., Ding, H., Angerer, J., Illig, T., Klopp, N., Bueno-de-Mesquita, B., Ros, M. M., Kaaks, R., Chang-Claude, J., Roswall, N., Tjønneland, A., Overvad, K., Clavel-Chapelon, F., Boutron-Ruault, M.-C., Dossus, L., Boeing, H., Weikert, S., Trichopoulos, D., Palli, D., Sieri, S., Tumino, R., Panico, S., Quirós, J. R., González, C., Sánchez, M. J., Dorronsoro, M., Navarro, C., Barricarte, A., Ljungberg, B., Johansson, M., Ulmert, D., Ehrnström, R., Khaw, K.-T., Wareham, N., Key, T. J., Ferrari, P., Romieu, I., Riboli, E., Brüning, T., & Vineis, P.
- Affiliations
- German Cancer Research Center (DE)
- Authors' Affiliations: 1Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Institute of the Ruhr University, Bochum; 2German Research Center for Environmental Health, Neuherberg; 3German Cancer Research Center (DKFZ), Heidelberg; 4Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Nuthetal; 5Department of Urology, University Hospital Charité, Berlin, Germany; 6The National Institute for Public Health and the Environment, Bilthoven; 7Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands; 8Danish Cancer Society Research Centre, Danish Cancer Society, Copenhagen; 9Department of Public Health, Institute of Epidemiology and Social Medicine, Aarhus, Denmark; 10INSERM, Centre for Research in Epidemiology and Population Health, Gustave Roussy Institute, Villejuif; 11Genetic Epidemiology Group; 12Nutritional Epidemiology Group, International Agency for Research on Cancer (IARC/WHO), Lyon
- Corresponding author
- Vineis, Paolo
- ORCID
- Rabstein, Sylvia
- Weiss, Tobias
- Casjens, Swaantje
- Rihs, Hans-Peter
- Ding, Hui
- Illig, Thomas
- Bueno-de-Mesquita, Bas
- Kaaks, Rudolf
- Chang-Claude, Jenny
- Roswall, Nina
- Tjønneland, Anne
- Overvad, Kim
- Dossus, Laure
- Weikert, Steffen
- Palli, Domenico
- Sieri, Sabina
- Tumino, Rosario
- Panico, Salvatore
- Quirós, José Ramón
- Navarro, Carmen
- Barricarte, Aurelio
- Ljungberg, Börje
- Johansson, Mattias
- Ulmert, David
- Khaw, Kay-Tee
- Key, Timothy J.
- Ferrari, Pietro
- Brüning, Thomas
- Vineis, Paolo
- Venue
- Cancer Epidemiology, Biomarkers & Prevention
- Published
- 2013-11-01
- Volume
- 22
- Issue
- 11
- Pages
- 2055-2065
- ISSN
- 1055-9965 (ISSN-L)
- 1538-7755
- OpenAlex
- W2056323305
- Cited by
- 35
- References
- 58
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 4 · 2022: 3 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 6 · 2014: 5
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Epidemiology Biomarkers & Prevention (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Site cant be reached (submittedVersion)
- Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
- Funders
- Cancer Research UK (14136)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- N-acetyltransferase 2, bladder cancer, occupational exposure, aromatic amines, polycyclic aromatic hydrocarbons, genetic susceptibility, smoking, job-exposure matrix, EPIC cohort
- MeSH terms
- Acetylation, Adult, Aged, Amines, Arylamine N-Acetyltransferase, Urinary Bladder Neoplasms, Female, Genotype, Humans, Male, Middle Aged, Phenotype, Polycyclic Aromatic Hydrocarbons, Risk Factors, Case-Control Studies, Occupational Exposure, Polymorphism, Single Nucleotide, Young Adult
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