Homologous recombination DNA repair gene RAD51, XRCC2 & XRCC3 polymorphisms and breast cancer risk in South Indian women

Taruna Rajagopal; Arun Seshachalam; Krishna Kumar Rathnam; Srikanth Talluri; Sivaramakrishnan Venkatabalasubramanian; Nageswara Rao Dunna

doi:10.1371/journal.pone.0259761

Homologous recombination DNA repair gene RAD51, XRCC2 & XRCC3 polymorphisms and breast cancer risk in South Indian women

PLoS One. 2022 Jan 21;17(1):e0259761. doi: 10.1371/journal.pone.0259761. eCollection 2022.

Authors

Taruna Rajagopal¹, Arun Seshachalam², Krishna Kumar Rathnam³, Srikanth Talluri^{4

5}, Sivaramakrishnan Venkatabalasubramanian⁶, Nageswara Rao Dunna¹

Affiliations

¹ Cancer Genomics Laboratory, Department of Biotechnology, School of Chemical and Biotechnology, SASTRA-Deemed University, Thanjavur, India.
² Department of Medical and Paediatric Oncology, Dr.G.V.N Cancer Institute, Singarathope, Trichy, India.
³ Department of Hemato Oncology-Medical Oncology and Bone Marrow Transplantation, Meenakshi Mission Hospital & Research Centre, Madurai, India.
⁴ Dana Farber Cancer Institute, Boston, MA, United States of America.
⁵ Veterans Administration Boston Healthcare System, West Roxbury, MA, United States of America.
⁶ Department of Genetic Engineering, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur Campus, Chennai, India.

Abstract

Background: Homologous recombination repair (HRR) accurately repairs the DNA double-strand breaks (DSBs) and is crucial for genome stability. Genetic polymorphisms in crucial HRR pathway genes might affect genome stability and promote tumorigenesis. Up to our knowledge, the present study is the first to investigate the impact of HRR gene polymorphisms on BC development in South Indian women. The present population-based case-control study investigated the association of polymorphisms in three key HRR genes (XRCC2-Arg188His, XRCC3-Thr241Met and RAD51-G135C) with BC risk.

Materials and methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping the HRR variants in 491 BC cases and 493 healthy women.

Results: We observed that the XRCC3 Met allele was significantly associated with BC risk [OR:1.27 (95% CI: 1.02-1.60); p = 0.035]. In addition, the homozygous mutant (C/C) genotype of RAD51 G135C variant conferred 2.19 fold elevated risk of BC [OR: 2.19 (95% CI: 1.06-4.54); p = 0.034]. Stratified analysis of HRR variants and BC clinicopathological features revealed that the XRCC3-Thr241Met and RAD51-G135C variants are associated with BC progression. Combined SNP analysis revealed that the individuals with RAD51-C/C, XRCC2-Arg/Arg, and XRCC3-Thr/Thr genotype combination have three-fold increased BC risk.

Conclusion: The present study imparts additional evidence that genetic variants in crucial HRR pathway genes might play a pivotal role in modulating BC risk in South Indian women.

MeSH terms

Adult
Breast Neoplasms* / genetics
Case-Control Studies
DNA-Binding Proteins* / genetics
Female
Genetic Predisposition to Disease*
Genotype
Humans
India / epidemiology
Middle Aged
Polymorphism, Single Nucleotide*
Rad51 Recombinase* / genetics
Recombinational DNA Repair* / genetics

Substances

X-ray repair cross complementing protein 3
Rad51 Recombinase
XRCC2 protein, human
DNA-Binding Proteins
RAD51 protein, human

Grants and funding

This study was funded by Department of Science and Technology, Science and Engineering Research Board (DST-SERB) (https://www.serbonline.in/SERB/HomePage), Government of India, Grant no. (YSS/2015/001692). The grant was awarded to Dr. Nageswara Rao Dunna. No (The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.).