The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case–control studies

Abstract

Background Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG + AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

Molecular Epidemiology in Amerindians of the Brazilian Amazon Reveals New Genetic Variants in DNA Repair Genes

“…The markers rs1799796 of the XRCC3 gene and rs184967 of the MSH3 gene were shown to be statistically significant regarding their distribution in the NAT population when compared to the AMR and EUR ones. The XRCC3 gene encodes a protein involved in the HRR pathway and in the repair of strand breaks caused by X-rays [ 11 , 46 ]. Based on the function of XRCC3, mutations in this gene are related to the development of various neoplastic types, such as osteosarcoma [ 47 ], bladder cancer [ 48 ], and thyroid cancer [ 9 ], among others [ 11 ].…”

“…In order to avoid these mutations, cells have evolved different DNA repair mechanisms to respond to specific damage and prevent mutagenesis [ 5 , 6 , 7 ]. There are at least four DNA repair mechanisms that have been well-described in humans: base excision repair (BER), nucleotide excision repair (NER), homologous recombination repair (HRR), and the mismatch/mismatch repair (MMR) pathway [ 8 , 9 , 10 , 11 ].…”

NBN, RAD51 and XRCC3 Polymorphisms as Potential Predictive Biomarkers of Adjuvant Radiotherapy Toxicity in Early HER2-Positive Breast Cancer

“…Still, the effect can differ among populations and cancer types [ 16 , 17 , 73 , 74 ]. XRCC3 rs1799794 was also associated with increased breast cancer risk [ 18 ]. According to the literature, RAD51 rs1801320 was also associated with increased risk for breast and other cancers, especially in carriers of BRCA2 mutations.…”

“…Our study focused on the genetic variability of key HRR genes previously reported in the literature [ 16 , 17 , 18 , 19 , 20 , 21 ]. Putatively functional tag single nucleotide polymorphisms (SNPs) in genes XRCC3 , RAD51 and NBN were selected based on the data from the International HapMap Project [ 35 ].…”

“…However, mutations in other HRR genes, such as ATM , CHEK2 , PALB2 , NBN , MRE11 , and RAD51 paralogs RAD51C and RAD51D also increase cancer risk and are already included in many screening panels for breast cancer [ 11 , 14 , 15 ]. Apart from rare mutations, several common single nucleotide polymorphisms (SNPs) in various HRR genes, including NBN , RAD51 , and XRCC3 , were reported to affect DNA repair capacity and were previously associated with altered breast cancer risk [ 16 , 17 , 18 , 19 , 20 , 21 ]. Genetic variability can also influence breast cancer treatment outcomes.…”