PhIP-induced chromosomal instability: A prostate cancer case-control study

2085

The heterocyclic amine 2 amino-1 methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), formed when meat containing food is cooked, has been implicated as an inducer of cancer of the colon, prostate and mammary gland in rats, tumors that are strongly associated with a Western diet. Humans have been found to be efficient metabolizers of the heterocyclic amines, generating species that are direct acting mutagens. Both exposures to carcinogens and individual susceptibility play significant roles in cancer risk. Suboptimal DNA repair, measured by quantifying mutagen-induced chromosome breaks, might explain variable host susceptibility to carcinogens. In this pilot case control study, we compared individual sensitivity to PhIP-induced chromosome breaks in short-term lymphocyte cultures from 116 study subjects, 56 prostate cancer patients and 60 age and ethnicity-matched healthy controls. Our results showed a significantly higher mean level of baseline spontaneous breaks in the PC patients compared to controls (mean + SE =1.74 + 0.33 and 0.89 + 0.18; p < 0.05). Similarly, PhIP induced a significantly higher level of breaks in the PC patients compared to controls (mean + SE = 5.34 + 0.52 and 3.85 + 0.28; p < 0.05). A significant association (R=0.550, p<0.001) between spontaneous and PhIP-induced breaks was observed. Such difference in the association was borderline significant (p=0.054) among the cases (R=0.597) and controls (R=0.310). The Poisson regression analysis was used to evaluate the relation between PhIP-induced chromosome aberrations and PC after controlling for the effects of baseline chromosome aberrations and other potential confounding factors such as, age, smoking status, BMI and family PC history. Our results indicate that PC cases had a 22-fold higher level of PhIP induced breaks than the controls (p<0.05) suggesting that PhIP may be a risk factor in development of PC.