Colorectal cancer risk in relation to genetic polymorphism of cytochrome P450 1A1, 2E1, and glutathione-S-transferase M1 enzymes

Chemical carcinogens generally require metabolic activation in order to be able to bind to DNA and contribute to cancer causation, Most of the human m etabolizing enzymes are genetically polymorphic, and these polymorphisms ma y affect the enzyme activity ol inducibility. In our present study we inves tigated the connection between genetic polymorphism of cytochrome P450 1A1, 2E1 (phase I enzymes) and glutathione-S-transferase MI (a phase II enzyme) and colorectal cancer occurence in a Hungarian population. The CYP 2E1 c2 allele proved to be in significant association with colorectal cancer (OR: 1.91, 95% CI: 1.05-3.52), rite CYP 1A1 Val allele was also overrepresented among colon cancer patients (OR: 1.57, 95% CI: 0.90-2.74), and the frequenc y of GSTM1 homozygous 0 genotype showed only minor difference (OR. 1.19, 95 % CI: 0.75-1.35). Combined analysis of the polymorphisms showed that indivi duals carrying all the three "high-risk" alleles have a strikingly increase d risk for sporadic colorectal cancer.