Human sensitivity to PhIP: a novel marker for prostate cancer risk.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been implicated in the development of colon, prostate and mammary gland tumors in rats. In this study, we developed a modified in vitro mutagen sensitivity assay, with activated PhIP (N-OH-PhIP) as the challenge mutagen and chromosome aberrations as the endpoint, and applied it in a pilot prostate cancer case-control study of 81 cases and 84 age and ethnicity-matched controls. Our results showed significantly higher baseline breaks among the cases, mean+/-S.E.=1.86+/-0.23 versus 0.96+/-0.14 in controls; P=0.006. Individuals with high baseline breaks (dichotomized at the control median) had a 36% increased risk for PC (OR=1.36; 95% CI=1.08-1.72). In stratified analysis, high baseline breaks was associated in younger participants (< or = 60 years) with an OR of 1.71 (1.14-2.57) and in those with a positive family history of PC, an OR of 1.43 (0.97-2.11). PhIP treatment induced significantly higher breaks in cases, mean+/-S.E.=5.07+/-0.39 versus 3.83+/-0.24 in controls; P=0.05. Higher PhIP-induced breaks was associated with an overall 17% increased risk for PC (OR=1.17; 95% CI=1.03-1.33), a significantly increased risks (OR=1.19; 95% CI=1.00-1.41) among younger participants, non-smokers (OR=1.39, 1.03-1.88) and 1.20 (1.00-1.45) among those with no family history of PC. Results from this pilot study demonstrate differential sensitivity to PhIP among subgroups and therefore, this assay have potential as a susceptibility marker for prostate cancer risk.