Red meat intake, NAT2, and risk of colorectal cancer: A pooled analysis of 11 studies

Ashwin N. Ananthakrishnan, Mengmeng Du, Sonja I. Berndt, Hermann Brenner, Bette J. Caan, Graham Casey, Jenny Chang-Claude, David Duggan, Charles S. Fuchs, Steven Gallinger, Edward L. Giovannucci, Tabitha A. Harrison, Richard B. Hayes, Michael Hoffmeister, John L. Hopper, Lifang Hou, Li Hsu, Mark A. Jenkins, Peter Kraft, Jing MaHongmei Nan, Polly A. Newcomb, Shuji Ogino, John D. Potter, Daniela Seminara, Martha L. Slattery, Mark Thornquist, Emily White, Kana Wu, Ulrike Peters, Andrew T. Chan

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27 Scopus citations

Abstract

Background: Red meat intake has been associated with risk of colorectal cancer, potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and colorectal cancer has been inconsistently reported. Methods:Weused pooled individual-level data from the Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium. Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results: From 11 studies, 8,290 colorectal cancer cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of colorectal cancer compared with the lowest quartile [OR, 1.41; 95% confidence interval (CI), 1.29-1.55].However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with colorectal cancer in those with a rapid/intermediate NAT2 genotype (OR, 1.38; 95% CI, 1.20-1.59) as with a slow genotype (OR, 1.43; 95% CI, 1.28-1.61; P interaction = 0.9). Conclusion:Wefound that high red meat intake was associated with increased risk of colorectal cancer only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact: Our results suggest no interaction between NAT2 genotype and red meat intake in mediating risk of colorectal cancer.

Original languageEnglish (US)
Pages (from-to)198-205
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2015

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Ananthakrishnan, A. N., Du, M., Berndt, S. I., Brenner, H., Caan, B. J., Casey, G., Chang-Claude, J., Duggan, D., Fuchs, C. S., Gallinger, S., Giovannucci, E. L., Harrison, T. A., Hayes, R. B., Hoffmeister, M., Hopper, J. L., Hou, L., Hsu, L., Jenkins, M. A., Kraft, P., ... Chan, A. T. (2015). Red meat intake, NAT2, and risk of colorectal cancer: A pooled analysis of 11 studies. Cancer Epidemiology Biomarkers and Prevention, 24(1), 198-205. https://doi.org/10.1158/1055-9965.EPI-14-0897