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Association between RAD51, XRCC2 and XRCC3 gene polymorphisms and risk of ovarian cancer: a case control and an in silico study

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Abstract

Homologous recombination (HR) is one of the important mechanisms in repairing double-strand breaks to maintain genomic integrity and DNA stability from the cytotoxic effects and mutations. Various studies have reported that single nucleotide polymorphisms (SNPs) in the HR-associated genes may have a significant association with ovarian cancer (OCa) risk but the results were inconclusive. In the present study, five polymorphisms of HR-associated genes (RAD51, XRCC2 and XRCC3) were genotyped by allelic discrimination assay in 200 OCa cases and 200 healthy individuals. The association with OCa risk was evaluated by unconditional logistic regression analyses. The results revealed that the mutant allele in both rs1801320 (CC) and rs1801321 (TT) of RAD51 gene was associated with increased risk of OCa (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.21–11.78, p = 0.014 and OR 1.61, 95% CI 1.06–2.45, p = 0.025, respectively). Moreover, a significant association of TT allele (OR 4.68, 95% CI 1.27–17.15, p = 0.011) of rs3218536 of XRCC2 gene with OCa was observed. Stratified analysis results showed that patients with early menarche and stages 3 and 4 were found to be associated with rs1801321 of RAD51 gene and rs1799794 of XRCC3 gene. In silico analysis predicted that the two missense SNPs (rs3218536 and rs1799794) were found to have an impact on the protein structure, stability and function. The present study suggested that RAD51 and XRCC2 gene polymorphisms might have an impact on the OCa risk in the South Indian population. However, studies with a larger sample and on different populations are needed to support the conclusions.

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Acknowledgements

All the authors are grateful to the Department of Biotechnology (DBT), India for the funding (Grant Number: 6242-P43/RGCB/PMD/DBT/ANDR/2015). We would like to thank all the study participants for volunteering to participate in this study. Also, we are grateful to nurses and staff in the Department of Oncology and Department of Obstetrics and Gynecology, SRIHER for providing samples and the data.

Funding

This work was supported by the Department of Biotechnology (DBT), India. (Grant Number: 6242-P43/RGCB/PMD/DBT/ANDR/2015).

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All the authors have a substantial role in this manuscript. This study was designed, directed and coordinated by GKG and AMF. GKG was involved in data collection, analysis, interpretation and writing the manuscript. AMF and SFDP helped in drafting the manuscript. JM, MM, NG, RR and UR provided the data for the study and validated results. SS has given input and validated results. All the authors read and approved the final version of the manuscript.

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Correspondence to Francis Andrea Mary.

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Gowtham Kumar, G., Paul, S.F.D., Martin, J. et al. Association between RAD51, XRCC2 and XRCC3 gene polymorphisms and risk of ovarian cancer: a case control and an in silico study. Mol Biol Rep 48, 4209–4220 (2021). https://doi.org/10.1007/s11033-021-06434-6

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