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

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Author

  • Beate Pesch
  • Katarzyna Gawrych
  • Sylvia Rabstein
  • Tobias Weiss
  • Swaantje Casjens
  • Hans-Peter Rihs
  • Hui Ding
  • Juergen Angerer
  • Thomas Illig
  • Norman Klopp
  • Bas Bueno-de-Mesquita
  • Martine M. Ros
  • Rudolf Kaaks
  • Jenny Chang-Claude
  • Nina Roswall
  • Anne Tjonneland
  • Kim Overvad
  • Francoise Clavel-Chapelon
  • Marie-Christine Boutron-Ruault
  • Laure Dossus
  • Heiner Boeing
  • Steffen Weikert
  • Dimitrios Trichopoulos
  • Domenico Palli
  • Sabina Sieri
  • Rosario Tumino
  • Salvatore Panico
  • Jose Ramon Quiros
  • Carlos Gonzalez
  • Maria Jose Sanchez
  • Miren Dorronsoro
  • Carmen Navarro
  • Aurelio Barricarte
  • Boerje Ljungberg
  • Mattias Johansson
  • David Ulmert
  • Roy Ehrnström
  • Kay-Tee Khaw
  • Nick Wareham
  • Timothy J. Key
  • Pietro Ferrari
  • Isabelle Romieu
  • Elio Riboli
  • Thomas Bruening
  • Paolo Vineis
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Summary, in English

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. (C) 2013 AACR.

Publishing year

2013

Language

English

Pages

2055-2065

Publication/Series

Cancer Epidemiology Biomarkers & Prevention

Volume

22

Issue

11

Document type

Journal article

Publisher

American Association for Cancer Research

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Urological cancer, Malmö
  • Pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 1538-7755