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Epidemiology and Prevention

A Prospective Study of N-Acetyltransferase Genotype, Red Meat Intake, and Risk of Colorectal Cancer

Jia Chen, Meir J. Stampfer, Heather L. Hough, Montserrat Garcia-Closas, Walter C. Willett, Charles H. Hennekens, Karl T. Kelsey and David J. Hunter
Jia Chen
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Meir J. Stampfer
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Heather L. Hough
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Montserrat Garcia-Closas
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Walter C. Willett
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Charles H. Hennekens
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Karl T. Kelsey
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David J. Hunter
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DOI:  Published August 1998
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Abstract

Carcinogenic heterocyclic amines are activated by N-acetyltransferase (NAT) enzymes, encoded by NAT1 and NAT2, to genotoxic compounds that can form DNA adducts in the colon epithelium. We have examined the relation of polymorphisms in the genes coding for both enzymes to risk of colorectal cancer and the gene-environment interaction with red meat intake among participants in the prospective Physicians' Health Study. Baseline blood samples from 212 men subsequently diagnosed with colorectal cancer during 13 years of follow-up were genotyped, along with 221 controls. NAT genotypes were analyzed by a PCR-restriction fragment length polymorphism method. Effect modification of the relation of red meat intake and risk of colorectal cancer by NAT genotype was assessed using conditional logistic regression. There was no overall independent association of NAT acetylation genotypes and colorectal cancer risk. The relative risks for the rapid acetylation genotype were 0.93 [95% confidence interval (CI), 0.61–1.42] for NAT1, 0.80 (95% CI, 0.53–1.19) for NAT2, and 0.81 (95% CI, 0.52–1.27) for NAT1/NAT2 combined. We observed a stronger association of red meat intake with cancer risk among NAT rapid acetylators, especially among men 60 years old or older. Among those men who were rapid acetylators for both NAT1 and NAT2, consumption of > 1 serving of red meat per day was associated with a relative risk of 5.82 (95% CI, 1.11–30.6) compared with consumption of ≤0.5 serving per day (P, trend = 0.02). These prospective data, which need to be confirmed in other studies, suggest that polymorphisms in the NAT genes confer differential susceptibility to the effect of red meat consumption on colorectal cancer risk.

Footnotes

  • ↵1 This study was supported by NIH Grants CA-70817, CA-72182, and CA-42182, J. C. is supported by NIH Training Grant ES07069. K. T. K. is supported by NIH Grant ES00002. D. J. H. is a recipient of American Cancer Society Faculty Research Award FRA-455.

  • ↵2 To whom requests for reprints should be addressed, at Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115. Phone: (617) 525-2043; Fax: (617) 525-2008; E-mail: jia.chen@channing.harvard.edu.

  • Received December 15, 1997.
  • Accepted May 29, 1998.
  • ©1998 American Association for Cancer Research.
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August 1998
Volume 58, Issue 15
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A Prospective Study of N-Acetyltransferase Genotype, Red Meat Intake, and Risk of Colorectal Cancer
Jia Chen, Meir J. Stampfer, Heather L. Hough, Montserrat Garcia-Closas, Walter C. Willett, Charles H. Hennekens, Karl T. Kelsey and David J. Hunter
Cancer Res August 1 1998 (58) (15) 3307-3311;

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A Prospective Study of N-Acetyltransferase Genotype, Red Meat Intake, and Risk of Colorectal Cancer
Jia Chen, Meir J. Stampfer, Heather L. Hough, Montserrat Garcia-Closas, Walter C. Willett, Charles H. Hennekens, Karl T. Kelsey and David J. Hunter
Cancer Res August 1 1998 (58) (15) 3307-3311;
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