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Heterocyclic amines (HAs)--potent mutagens formed as red meat, chicken or fish cooks--cause cancer at multiple sites (including rat prostate) in rodent bioassays, and have been linked to elevated human risk of colon and other cancers. Compared to white men in the U.S., African American (AA) men have about twice the prostate cancer (PC) incidence and about twice the daily intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the predominant HA in the U.S. diet. To investigate the hypothesis that dietary PhIP exposure increases PC risk, an ongoing prospective clinic-based study has compared PC-screening outcomes with survey-based estimates of dietary PhIP intake by 40- to 70-year-old AA men in the Oakland, CA, area. Participants with no prior PC diagnosis, recruited through a cancer education center/screening clinic, complete food-frequency and meat-cooking/consumption questionnaires, and have a prostate-specifc antigen (PSA) test and digital-rectal exam. Preliminary results for 562 participants indicate that mean (±1 SD) daily intake of PhIP, the major HA found in cooked meats, in this group is 19 (±24) ng kg-1 d-1, which is ~2-fold (and ~3-fold) greater than a national estimate of mean PhIP intake for AA (and white U.S.) men of similar age. In the present study, estimated PhIP intakes were found to be attributable mostly (65%) to chicken and positively associated (R2 = 0.25, p ~ 0) with estimated saturated fat (SF) intake (a previously hypothesized environmental PC-risk factor). An odds ratio, OR, (and maximum-likelihood 95% confidence limits) of 23.6 (2.20, 533.) for PSA ≥20 ng/mL was observed for those in the highest 15% compared to the lower 50% of estimated daily PhIP intakes (≥32 vs. ≤4.8 ng kg-1 d-1), with a p-value (ptrend) of 0.0023 for a chi-square test for trend done across three (including these two) PhIP-intake groups (extended Fisher exact test p-value = 0.0063). This positive trend persisted after separate adjustments for self-reported family (brother or father) history of PC (FH), SF intake, and energy intake (ptrend = 0.0024, 0.012, and 0.0032, respectively). PSA measures were found (by Kolmogorov 2-sample tests) to be significantly higher in AA men reporting a positive FH in this study (p = 0.007), particularly for those among the highest PSA-measure quartile in each FH group (p < 0.0002). These preliminary results are consistent with a positive association between PhIP intake and highly elevated PSA levels, supporting the hypothesis that diet and food preparation interventions may help reduce PC risk in AA and perhaps other groups.

[Work performed under auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under contract No. W-7405-Eng-48, and the University of California San Francisco, with funding by the National Cancer Institute (NIH grant P01 CA55861-01) and Department of Defense (PCRP grant PC040371).]

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA