Abstract
We aimed to investigate the effect of hotspot variations of XRCC2 gene on the risk of head and neck cancer (HNC) in 400 patients and 400 controls. Five polymorphisms of XRCC2 gene G4234C (rs3218384), G4088T (rs3218373), G3063A (rs2040639), R188H (rs3218536) and rs7802034 were analyzed using Allele- specific polymerase chain reaction (ARMS-PCR) followed by sequence analysis. For rs3218373, the GG genotype indicated a statistically significant 3-fold increased risk of HNC (P < 0.001) after multivariate adjustment. For rs7802034, the GG genotype suggested statistically significant 2-fold increased risk of HNC (P < 0.001). For SNP of rs3218536, the AA genotype indicated a significant 3-fold increased risk of HNC (P < 0.001). Additionally, haplotype analysis revealed that TACAG, TGGAG, TACGG and TAGGA haplotypes of XRCC2 polymorphisms are associated with HNC risk. Two SNPs in XRCC2 (rs2040639 and rs3218384) were found increased in strong linkage disequilibrium. Furthermore, joint effect model showed 20 fold (OR = 19.89; 95% CI = 2.65–149.36, P = 0.003) increased HNC risk in patients carrying four homozygous risk alleles of selected polymorphisms. These results show that allele distributions and genotypes of XRCC2 SNPs are significantly associated with increased HNC risk and could be a genetic adjuster for the said disease.
Highlights
Various damaging agents such as chemicals, radiations and some endogenous elements affect DNA integrity which result in single strand breaks (SSBs)
Single nucleotide polymorphisms have been identified in these DNA repair genes, such as X-ray repair cross complementing group 2 (XRCC2), but the influence of specific genetic variants on repair phenotype and cancer risk has not yet been identified[27,28,29,30,31]
An attempt was undertaken in this study to determine whether single nucleotide polymorphisms (SNPs) in XRCC2 gene are associated with head and neck cancer
Summary
Various damaging agents such as chemicals, radiations and some endogenous elements affect DNA integrity which result in single strand breaks (SSBs). X-ray repair cross complementing group 2 (XRCC2) gene, XRCC2 protein, together with other proteins of RAD516, forms a complex which plays a critical role in chromosomal segregation and apoptotic response to DSBs7. This crucial function of the XRCC2 protein for the HRR process has been demonstrated in earlier studies where over 100 fold HRR reduction in XRCC2 deficient hamster cells was observed compared to parental cells[8]. Since XRCC2 genomic sequence is highly polymorphic, it is of interest to identify genetic defects which have a functional potential to affect the final repairing efficiency of XRCC2, and subsequently the development of head and neck cancer. On the basis of these observations, it was planned to study the role of XRCC2 gene as a candidate involved in the underlying cause of head and neck carcinogenesis
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