A Meta-Analysis for Association of XRCC1, XRCC2 and XRCC3 Polymorphisms with Susceptibility to Thyroid Cancer

Abstract

Background:We conducted a comprehensive meta-analysis to explore the association of polymorphisms at XRCC1, XRCC2 and XRCC3 genes with susceptibility to thyroid cancer (TC). Methods: We searched PubMed, EMBASE, Web of Science, and CNKI for relevant available studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Results: A total of 67 studies including 17 studies with 6,806 cases and 5,229 controls on XRCC1 Arg399Gln, 13 studies with 3,234 cases and 4,807 controls on XRCC1 Arg280His, 13 studies with 2,956 cases and 3,860 controls on XRCC1 Arg194Trp, five studies with 1,287 cases and 1,422 controls on XRCC2 Arg188His, 13 studies with 2,488 cases and 3,586 controls on XRCC3 Thr241Met, and six studies with 1,828 cases and 2,060 controls on XRCC3 IVS5-14 polymorphism were selected. Polled data revealed that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His and XRCC3 Thr241Met and IVS5-14 polymorphisms were not significantly associated with an increased risk of TC. Stratified analyses by ethnicity showed that the XRCC1 Arg399Gln polymorphism was associated with TC risk in Caucasians, but not in Asians. Conclusions: Our meta-analysis indicated that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met and IVS5-14 polymorphisms were not associated with risk of TC in the global population. Further well-designed investigations with large sample sizes are required to confirm our results.

Association between XRCC2 Arg188His Polymorphism and Breast Cancer Susceptibility: A Systematic Review and Meta-Analysis

“…The X-ray repair cross-complementing 2 (XRCC2) gene, located at 7q36.1, is a member of the RecA/Rad51related protein family that participates in homologous recombination repair (HRR) to maintain chromosome stability and repair DNA damage [13,[20][21][22][23]. Thus, XRCC2 is a functional candidate for involvement in cancer progression [24][25][26].…”

Polymorphisms of DNA Repair Genes in Thyroid Cancer

“…The results of several meta-analyses yielded conflicting results, suggesting the complexity of the association between XRCC1 polymorphisms and thyroid cancer risk depending on ethnicity. Mandegari et al conducted a meta-analysis on polymorphisms in the XRCC1 gene—rs25487, rs25489, and rs1799782—and did not demonstrate a significant association with the risk of thyroid cancer [ 38 ]. However, subgroup analysis suggested an association of rs25487 with the risk of thyroid cancer in Caucasians but not in the Asian population.…”

“…However, a polygenic risk analysis, taking into account genotype combinations of different DNA repair genes, including RAD52 (CC)/ XRCC2 (GG)/ XRCC3 (CT + TT) (OR = 2.204; 95% CI = 1.08–4.51; p = 0.029), have indicated positive association where the combined variant RAD52 / XRCC2 / XRCC3 showed a significant five-fold increase in the risk of thyroid cancer compared to the wild type (OR = 5.04; 95% CI = 1.45–17.58; p = 0.007) [ 43 ]. However, the overall and combined meta-analyses showed that the XRCC2 rs3218536 polymorphism was not significantly associated with the risk of thyroid cancer [ 38 , 45 ]. The genotypic frequencies of selected SNPs of the XRCC2 gene in various populations and their associations with the risk of thyroid cancer are presented in Table 2 .…”

“…The results of meta-analyses regarding polymorphisms of the XRCC3 gene in thyroid cancer are mixed. According to Mandegari et al, rs1799796 and rs861539 in XRCC3 did not show a significant relationship with the risk of thyroid cancer [ 38 ]. The ethnic subgroup analyses did not confirm a significant association between rs861539 and the risk of thyroid cancer in Asians and Caucasians.…”