Background: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair)pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repairefficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene(at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity andincreased genomic instability in multiple studies. Hence our investigation focused on genotyping these variantsto correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that thesevariants of the XRCC1 gene might influence disease susceptibility. Materials and
Methods: We examined thefrequency of the polymorphism in one hundred cases and an almost equal number of controls after recordingtheir demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCRstudies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed.
Results: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%),and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln toshow association with lung cancer. Correlating these genotypes with several parameters, we also found that thesetwo variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Glngenotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenariowhere Arg399Gln genotypes were found to be associated with stage of the disease in females.
Conclusions: Itis concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients withsmoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lungcancer for diagnosis and prognosis.