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

About this Publication
Title
Red meat intake, NAT2, and risk of colorectal cancer: a pooled analysis of 11 studies.
Pubmed ID
25342387 (View this publication on the PubMed website)
Publication
Cancer Epidemiol. Biomarkers Prev. 2015 Jan; Volume 24 (Issue 1): Pages 198-205
Authors
Ananthakrishnan AN, Du M, Berndt SI, Brenner H, Caan BJ, Casey G, Chang-Claude J, Duggan D, Fuchs CS, Gallinger S, Giovannucci EL, Harrison TA, Hayes RB, Hoffmeister M, Hopper JL, Hou L, Hsu L, Jenkins MA, Kraft P, Ma J, ...show more Nan H, Newcomb PA, Ogino S, Potter JD, Seminara D, Slattery ML, Thornquist M, White E, Wu K, Peters U, Chan AT
Affiliations
  • Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. German Cancer Consortium, Heidelberg, Germany.
  • Kaiser Permanente Medical Care, Oakland, CA.
  • University of Southern California, Los Angeles, California.
  • German Cancer Consortium, Heidelberg, Germany. Division of Cancer Epidemiology, German Cancer Research Center (DFKZ), Heidelberg, Germany.
  • Translational Genomics Research Institute, Phoenix, Arizona.
  • Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts. Channing Division of Network Medicine, Boston, Massachusetts.
  • Mount Sinai Hospital and University Health Network Toronto General Hospital, Toronto, Canada.
...show more
  • Channing Division of Network Medicine, Boston, Massachusetts. Harvard School of Public Health, Boston, Massachusetts.
  • New York University School of Medicine, New York, New York.
  • German Cancer Consortium, Heidelberg, Germany.
  • Melbourne School of Population Health, The University of Melbourne, Australia.
  • Department of Preventive Medicine and The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Evanston, Illinois.
  • Harvard School of Public Health, Boston, Massachusetts.
  • Department of Epidemiology, Richard M. Fairbanks School of Public Health, Simon Cancer Center, Indiana University, Indianapolis, Indiana.
  • Channing Division of Network Medicine, Boston, Massachusetts. Harvard School of Public Health, Boston, Massachusetts. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Fred Hutchinson Cancer Research Center, Seattle, Washington. University of Washington School of Public Health, Seattle, Washington. Centre for Public Health Research, Massey University, Wellington, New Zealand.
  • University of Utah Health Sciences, Salt Lake City, Utah.
  • Fred Hutchinson Cancer Research Center, Seattle, Washington. University of Washington School of Public Health, Seattle, Washington. achan@mgh.harvard.edu upeters@fhcrc.org.
  • Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. achan@mgh.harvard.edu upeters@fhcrc.org.
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: We used 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: We found 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.

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