Sequence Polymorphism in Xenobiotic Metabolising Genes in Iraqi Colorectal Cancer Patients

OBJECTIVES: Colorectal cancer (CRC) is the third most prevalent malignant neoplasm. Genetic variations in the xenobiotic metabolising cytochrome enzymes. Family 1 Subfamily A Member 1 (CYP1A1) and Family 1 Subfamily B Member 1 (CYP1B1) might play a role in cancer pathogenesis and prognosis. The aim of this work is to determine the frequency of Single Nucleotide Polymorphisms (SNPs) in CYP1A1 (rs1048943, Ile462VaI and rs4646903/MSP1) and CYP1B1 (rs1056836, Leu432Val) genes in patients with CRC cancer. It was also an attempt to identify the association between SNPs and CRC and its stage and grade at diagnosis. METHODS: This case-control study was conducted in Kirkuk/Iraq, 200 patients with CRC and 200 cancer free control subjects were enrolled. Genomic DNA was extracted from venous blood samples and screened for SNPs using Restriction Fragment Length Polymorphism (RFLP) and confirmed by the direct DNA sequencing. RESULTS: The reference genotype of CYP1A1 gene rs1048943 is AA. Both the AG and GG variants were significantly more frequent in the cancer group and associated with increased risks of CRC and its later stages (stages III and IV) and poor differentiation (p<0.01). The reference genotype of CYP1A1 rs4646903 is TT. The variant genotypes, TC and CC, had no significant association with increased odds of cancer (P>0.05) or with tumour stage or its grade (p>0.05). The GG genotype of CYP1B1 rs1056836 was the reference genotype. The CG and CC variants were not associated with increased risks of CRC (P>0.05) or its stage or grade except the CG genotype which was associated with poor differentiation (OR= 3.4, 95 % CI= 1.8 -6.5, P<0.001). CONCLUSION: CYP1A1 gene rs1048943 SNPs can represent a potential future marker for CRC risk prediction and prognosis. Further evaluation in large scale studies will provide greater understanding of the effects of other genes SNPs on CRC risk and prognosis.