Single nucleotide polymorphisms of nucleotide excision repair and homologous recombination repair pathways and their role in the risk of osteosarcoma.

Jiapeng Yin

doi:10.12669/pjms.312.6569

Abstract

Objective:To evaluate the influence of polymorphisms in nucleotide excision repair (NER) and homologous recombination repair (HRR) pathways on the development of osteosarcoma patients.Methods:Genotypes of ERCC1 rs11615 and rs3212986, ERCC2 rs1799793 and rs13181, NBN rs709816 and rs1805794, RAD51 rs1801320, rs1801321 and rs12593359, and XRCC3 rs861539 were conducted by Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) assay.Results:Total 148 osteosarcoma patients and 296 control subjects were collected from Taizhou First People’s Hospital. Conditional logistic regression analyses found that individuals carrying with GA+AA genotype of ERCC2 rs1799793 and GC+CC genotype of NBN rs1805794 were significantly associated with increased risk of osteosarcoma, and the ORs(95%CI) were 1.58(1.03-2.41) and 2.66(1.73-4.08), respectively. We found that GA+AA genotype of ERCC2 rs1799793 or GC+CC genotype of NBN rs1805794 were associated with an increased risk of osteosarcoma in females, with ORs(95%CI) of 2.42(1.20-4.87) and 2.01(1.07-4.23), respectively.Conclusion:Our results suggest that ERCC2 rs1799793 and NBN rs1805794 polymorphisms were associated with an increased risk for osteosarcoma, which suggests that NER and HRR pathways modulate the risk of developing osteosarcoma.

Highlights

Osteosarcoma is a rare bone cancer that has a first peak of incidence in adolescents around 16 years, and a second peak in patients older than 60 years.[1]
We found that GA+AA genotype of Excision repair cross-complementation group 2 (ERCC2) rs1799793 or GC+CC genotype of NBN rs1805794 were associated with an increased risk of osteosarcoma in females, and the odds ratio (OR)(95%confidence intervals (CI)) were 2.42(1.20-4.87) and 2.01(1.074.23), respectively
In this hospital-based case-control study, we investigated the role of ten SNPs in nucleotide excision repair (NER) and homologous recombination repair (HRR) pathways about the risk of osteosarcoma

Summary

Introduction

Osteosarcoma is a rare bone cancer that has a first peak of incidence in adolescents around 16 years, and a second peak in patients older than 60 years.[1]. Genetic polymorphisms in DNA repair genes may lead to amino acid substitution and cause differential capacity to repair DNA damage. The genetic polymorphisms in DNA repair genes have been found to be associated with increased genetic instability and carcinogenesis.[5] In mammalian cells, there were four different DNA repair mechanisms, including nucleotide excision repair (NER), homologous recombination repair (HRR), doublestrand break repair (DSBR) and mismatch repair.[6,7] All these DNA repair pathways are finely regulated for the maintenance of genomic integrity and modulation of repair capacity in response to DNA damage and susceptibility to cancer risk

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Results

Conclusion