The Codon 399 Arg/Gln XRCC1 Polymorphism is Associated with Lung Cancer in Indians

Abstract

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 repair efficiency 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 and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility. Materials and Methods: We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, 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 to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Gln genotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenario where Arg399Gln genotypes were found to be associated with stage of the disease in females. Conclusions: It is concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients with smoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lung cancer for diagnosis and prognosis.

Expression of ERCC1, RRM1 and LRP in Non-small Cell Lung Cancers and their Influence on Chemotherapeutic Efficacy of Gemcitabine Concomitant with Nedaplatin

“…Lung cancers rank the top of cancer-related death with increasing morbidity around the world (Aydiner et al, 2013;Cai et al, 2013;Kaya et al, 2013;Mutlu et al, 2013;Natukula et al, 2013;Oven et al, 2013;Unal et al, 2013;Wang et al, 2013). At present, the chemotherapeutic protocols for NSCLC mainly apply platinums as basic drugs combining with the third generation chemotherapeutic drugs such as paclitaxel, gemcitabine and vinorelbine, etc..…”

Association of TNFα−308, IFNγ+874, and IL10−1082 gene polymorphisms and the risk of non-small cell lung cancer in the population of the South Indian state of Telangana

“…Gene polymorphisms and their contributions to risk and disease progression in NSCLC have been reported: examples include matrix metalloproteases [24], epidermal growth factor receptors [25], cyclins [26], hydrolytic enzymes [27], bone morphogenetic proteins [28], and cytokines [12,16,17]. In the Indian context, polymorphisms in XRCC1, p53, N-acetylation 2, EGFR, and UGT genes were reported to augment lung cancer susceptibility [29]. However, there are no reports that correlate the association of cytokine gene polymorphisms and NSCLC risk in the Indian population, except for one report that suggests a dearth of association between the IL-8 gene polymorphism and NSCLC in the population of Kashmir valley [30].…”

Pharmacogenomics Influencing Drug-Gene Interactions Leading Towards Personalized Medicine

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