CYP1AJ Genetic Polymorphisms and in Situ Colorectal Cancer1

cently, with colorectal cancer (8). Thus, it is conceivable that PAHs play a role in some of the genetic alterations leading to colorectal tumor development. CYP1A1 is of critical importance for the metabolism of PAHs. The gene product, AHH, initiates a multienzyme pathway that converts PAHs to their ultimate DNA-binding carcinogenic forms. A MspI RFLP of the 3'-end of the human CYPIAJ gene has recently been described which is in genetic disequilibrium with an adenine to guanine mutation at residue 462 in exon 7. The latter mutation causes an isoleucine to valine substitution in the heme binding region of CYPJA1, which appears to result in an increased enzymatic activity (9).Thesetwopolymorphisms havebeenshowntobemorefrequent in Japanese than in Caucasians and to be associated with lung cancer (10, 11). In the present study, we assessed these CYP1A1 polymor phisms in a population-based case-control study of in situ colorectal cancer and found that they may also be associated with large bowel cancer.