Polymorphism of Selected Genes Coding for Xenobiotic-Metabolizing Enzymes and Susceptibility to Colorectal Cancer in a Saudi Population

Abstract

Colorectal cancer (CRC) is a threatening health problem in Saudi Arabia. Polymorphism of genes coding for xenobiotic-metabolizing enzymes (XME) represent significant risk for a variety of cancers related to the interaction of environmental and genetic factors. The present study aimed to investigate the contribution of CYP1A1 and NAT2 genes polymorphism in CRC. We conducted a hospital-based case-control study in Saudi population. Samples from buccal swabs were obtained from 116 de novo diagnosed cases of CRC and 72 controls. Seven polymorphisms in the two genes analysed: CYP1A1 T3801C, CYP1A1 C2453A, CYP1A1 A2455G, NAT2 G590A, NAT2 C481T, NAT2 G857A, and NAT2 A803G were identified. Among selected genes, CYP1A1 A2455G and NAT2 A803G genotypes demonstrated significant differences (p<0.05, 0.001) and greater risk for developing CRC comparing to the wild genotype (OR: 7.65, 12.13 and 8.18 for GA, AA and GA+AA respectively for CYP1A1 A2455G; and 3.65, 4.24 and 4.17 for GA, GG and GA+GG respectively for NAT2 A803G). Remaining loci demonstrated no significance with risk. Of the seven polymorphisms screened, CYP1A1 A2455G and NAT2 A803G may be of importance to the colon carcinogenesis. Further large-scale studies are needed.