Distribution of genetic polymorphisms of nucleotide excision repair genes and risk of gastrointestinal cancer: Findings from a case-control study.

Background: Gastrointestinal cancer (GI) is one of the most common and deadly cancers worldwide. In the present study, we assessed the association between single nucleotide polymorphisms (SNPs) within nucleotide excision repair (NER) pathway genes (xeroderma pigmentosum complementation group C [XPC], xeroderma pigmentosum complementation group G [XPG], and xeroderma pigmentosum complementation group D [XPD]) and the GI cancer risk in the rural population of Maharashtra.

Methods: The genotyping of XPC, XPD, and XPG genes was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using 200 clinically confirmed GI cancer cases and equal number of healthy controls. The association of polymorphisms was confirmed by odds ratio (OR) with 95% confidence interval (CI).

Results: The frequency distribution of XPD gene (C22541A) polymorphism showed that variant A/A genotype increased four times (OR = 4.08; 95% CI = 2.14-7.77; P: < 0.0001) and G23591A polymorphism with heterozygous G/A genotype showed significant correlation (OR = 6.90; 95% CI = 4.28-11.11; P < 0.0001) with risk of GI cancer compared to variant A/A genotype (OR = 1.92; 95% CI = 1.00-3.69; P = 0.04). The results of genetic association analysis of XPC at codon 939 of exon 15 and XPG at codon 1104 of exon 15 showed no association with GI cancer risk in the studied population.

Conclusion: Our results indicated that XPD Arg156Arg and Asp312Asn polymorphisms were significantly associated with GI cancer risk whereas XPC Lys939Gln and XPG His1104Asp polymorphisms were not statistically significant.