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Meat cooked at high temperatures, using techniques such as frying and grilling, produces high levels of heterocyclic amines (HCAs). Evidence from rodent models has shown that a high intake of HCAs, specifically PhIP, results in prostate tumors. This study investigated dietary intake of meat, meat cooking and preserving methods and HCAs as risk factors for prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Usual dietary intake was assessed using a 137-item food frequency questionnaire and a detailed meat cooking questionnaire. The three most abundant mutagenic HCAs found in cooked meat are 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The intake of these three HCAs was assessed by linking the meat-cooking questionnaire to a database specifically developed to determine human exposure to these compounds. Of 29,361 men aged 55-74 years, 1338 developed prostate cancer during 121,938 person-years of follow-up, by October 1st, 2001. Multivariate analyses were conducted using a Cox’s proportional hazards model. No associations were observed for total meat, red meat or white meat intake and prostate cancer risk. However, processed meats, which included luncheon meats, bacon and sausage, showed a significant 64% increased risk of advanced prostate cancer (Gleason score > 8 or Stage III or IV tumors, n=263)), comparing the highest quintile with the lowest quintile (95% confidence interval of 1.06-2.55). Intake of MeIQx and DiMeIQx were not associated with prostate cancer risk. However, PhIP significantly increased the risk of prostate cancer (relative risk: 1.22, 95% confidence interval: 1.01-1.48) particularly if restricted to cases diagnosed at least one year after enrollment (n=868, relative risk: 1.27, 95% confidence interval: 1.01-1.61) comparing men in the highest to those in the lowest quintile of PhIP intake. This prospective study of meat and meat mutagens shows that processed meat increases the risk of advanced prostate cancer and also lends epidemiologic support to the animal studies which have implicated PhIP as a prostate carcinogen.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]