title: Red meat intake, NAT2, and risk of colorectal cancer: a pooled analysis of 11 studies.
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).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Our results suggest no interaction between NAT2 genotype and red meat intake in mediating risk of colorectal cancer.
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Ashwin N
authors.initials: AN
authors.lastname: Ananthakrishnan
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Mengmeng
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authors.lastname: Du
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. German Cancer Consortium, Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.affiliation: Kaiser Permanente Medical Care, Oakland, CA.
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
authors.affiliation: University of Southern California, Los Angeles, California.
authors.forename: Graham
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authors.lastname: Casey
authors.affiliation: German Cancer Consortium, Heidelberg, Germany. Division of Cancer Epidemiology, German Cancer Research Center (DFKZ), Heidelberg, Germany.
authors.forename: Jenny
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authors.lastname: Chang-Claude
authors.affiliation: Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: David
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authors.lastname: Duggan
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts. Channing Division of Network Medicine, Boston, Massachusetts.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Mount Sinai Hospital and University Health Network Toronto General Hospital, Toronto, Canada.
authors.forename: Steven
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authors.lastname: Gallinger
authors.affiliation: Channing Division of Network Medicine, Boston, Massachusetts. Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Tabitha A
authors.initials: TA
authors.lastname: Harrison
authors.affiliation: New York University School of Medicine, New York, New York.
authors.forename: Richard B
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authors.lastname: Hayes
authors.affiliation: German Cancer Consortium, Heidelberg, Germany.
authors.forename: Michael
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authors.lastname: Hoffmeister
authors.affiliation: Melbourne School of Population Health, The University of Melbourne, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Department of Preventive Medicine and The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Evanston, Illinois.
authors.forename: Lifang
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authors.lastname: Hou
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Li
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authors.lastname: Hsu
authors.affiliation: Melbourne School of Population Health, The University of Melbourne, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Peter
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authors.lastname: Kraft
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts. Channing Division of Network Medicine, Boston, Massachusetts.
authors.forename: Jing
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authors.lastname: Ma
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Simon Cancer Center, Indiana University, Indianapolis, Indiana.
authors.forename: Hongmei
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authors.lastname: Nan
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: 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.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
authors.affiliation: 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.
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Daniela
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authors.lastname: Seminara
authors.affiliation: University of Utah Health Sciences, Salt Lake City, Utah.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Mark
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authors.lastname: Thornquist
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.affiliation: Channing Division of Network Medicine, Boston, Massachusetts. Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Kana
authors.initials: K
authors.lastname: Wu
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington. University of Washington School of Public Health, Seattle, Washington. achan@mgh.harvard.edu upeters@fhcrc.org.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. achan@mgh.harvard.edu upeters@fhcrc.org.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000009:adverse effects*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000209:etiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008460:Meat / Q000009:adverse effects*; D008875:Middle Aged; D011786:Quality Control; D012307:Risk Factors
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human