A Prospective Study of Meat and Meat Mutagens and Prostate Cancer Risk

  1. Rashmi Sinha1
  1. 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland; 2Fred Hutchinson Cancer Research Center, Seattle, Washington; 3Division of Preventive Oncology, Cancer Care Ontario, Toronto, Ontario, Canada; 4Washington University, St. Louis, Missouri; and 5Marshfield Clinic Research Foundation, Marshfield, Wisconsin
  1. Requests for reprints:
    Amanda J. Cross, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Rockville, MD 20852. Phone: 301-496-4378; Fax: 301-496-6829; E-mail: crossa{at}mail.nih.gov.

Abstract

High-temperature cooked meat contains heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP). In rodents, a high intake of PhIP induces prostate tumors. We prospectively investigated the association between meat and meat mutagens, specifically PhIP, and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Diet was assessed using a 137-item food frequency questionnaire and a detailed meat-cooking questionnaire linked to a database for BaP and the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and PhIP. During follow-up, we ascertained a total of 1,338 prostate cancer cases among 29,361 men; of these, 868 were incident cases (diagnosed after the first year of follow-up) and 520 were advanced cases (stage III or IV or a Gleason score of ≥7). Total, red, or white meat intake was not associated with prostate cancer risk. More than 10 g/d of very well done meat, compared with no consumption, was associated with a 1.4-fold increased risk of prostate cancer [95% confidence interval (95% CI), 1.05-1.92] and a 1.7-fold increased risk (95% CI, 1.19-2.40) of incident disease. Although there was no association with MeIQx and DiMeIQx, the highest quintile of PhIP was associated with a 1.2-fold increased risk of prostate cancer (95% CI, 1.01-1.48) and a 1.3-fold increased risk of incident disease (95% CI, 1.01-1.61). In conclusion, very well done meat was positively associated with prostate cancer risk. In addition, this study lends epidemiologic support to the animal studies, which have implicated PhIP as a prostate carcinogen. (Cancer Res 2005; 65(24): 11779-84)

Footnotes

  • Received June 22, 2005.
  • Accepted September 29, 2005.
  • Revision received September 6, 2005.
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