Journal Article

Meat-related mutagen exposure, xenobiotic metabolizing gene polymorphisms and the risk of advanced colorectal adenoma and cancer

Anne M.J. Gilsing, Sonja I Berndt, Elizabeth 
H Ruder, Barry I Graubard, Leah M Ferrucci, Laura Burdett, Joel L. Weissfeld, Amanda J Cross and Rashmi Sinha

in Carcinogenesis

Volume 33, issue 7, pages 1332-1339
Published in print July 2012 | ISSN: 0143-3334
Published online May 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs158
Meat-related mutagen exposure, xenobiotic metabolizing gene polymorphisms and the risk of advanced colorectal adenoma and cancer

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Meat mutagens, including heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds (NOCs), may be involved in colorectal carcinogenesis depending on their activation or detoxification by phase I and II xenobiotic metabolizing enzymes (XME). Using unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), we examined the intake of five meat mutagens and >300 single nucleotide polymorphisms (SNPs) in 18 XME genes in relation to advanced colorectal adenoma (1205 cases and 1387 controls) and colorectal cancer (370 cases and 401 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary intake of meat mutagens was assessed using a food frequency questionnaire with a detailed meat-cooking module. An interaction was observed between 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intake and the NAT1 polymorphism rs6586714 in the adenoma study (P interaction = 0.001). Among individuals carrying a GG genotype, high MeIQx intake was associated with a 43% increased risk of adenoma (95% CI 1.11–1.85, P trend = 0.07), whereas the reverse was observed among carriers of the A variant (OR = 0.50, 95% CI 0.30–0.84, P trend = 0.01). In addition, we observed some suggestive (P < 0.05) modifying effects for SNPs in other XME genes (UGT1A, CYP2E1, EPHX1, AHR and GSTM3), but these were not significant after adjustment for multiple testing. This large and comprehensive study of XME genes, meat mutagens and the risk of colorectal tumours found that a NAT1 polymorphism modified the association between MeIQx intake and colorectal adenoma risk.

Journal Article.  6884 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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