Association Studies Between XRCC1, XRCC2, XRCC3 Polymorphisms and Differentiated Thyroid Carcinoma

Abstract

Background/Aims: DNA HRR pathway and BER pathway play vital roles in differentiated thyroid cancer (DTC) development, thus we supposed that polymorphisms of XRCC1, XRCC2, XRCC3 DNA repair genes are associated with thyroid cancer risk and progression. Methods: We searched the NCBI database for relevant literatures to determine eight SNPs to be included in our study (XRCC1: rs25487, rs25489, rs1799782; XRCC2: rs3218536; XRCC3: rs1799794, rs56377012, rs1799796, rs861539). Results: SNP of rs25487 was linked with a 53% decrease in DTC risk (OR: 0.47; 95%CI: 0.268-0.82; P = 0.01). For SNP of rs1799782, the homozygous TT genotype indicated a statistically significant 2-fold increased risk of DTC (OR: 2.09; 95%CI: 1.27-3.43; P < 0.001) after multivariate adjustment. For SNP of rs861539, the homozygous TT genotype suggested statistically significant 3-fold increased risk of DTC (OR: 3.02; 95%CI: 1.68-5.42; P < 0.001). No significant association between the other five SNPs and DTC risk. Besides that, female was linked with 47% increase in DTC risk (OR: 1.47; 95%CI: 1.062-2.04; P = 0.02) after multivariate adjustment. Similar results for most of the SNPs were obtained from subgroup analysis by different histological types of DTC. Haplotype analysis revealed that AGC and GGT haplotypes of XRCC1 polymorphisms were associated with DTC. Moreover, results from gene-gene interaction showed that XRCC1-rs25487, XRCC1- rs1799782 and XRCC3- rs861539 variants jointly contributed to a specifically increased risk of DTC, with the combination variant of rs1799782-CT heterozygote and rs861539-TT homozygote exhibiting a higher 3.66-fold risk of DTC (OR: 3.66; 95% CI: 1.476-9.091, P = 0.005). Conclusion: Polymorphisms of XRCC1 (rs25487, rs1799782) and XRCC3 (rs861539), may play a critical role in DTC development and progression. Furthermore, XRCC1 variant can interact with XRCC3 variant to significantly increase DTC susceptibility. Identifying these genetic risk markers could provide evidence for exploring the insight pathogenesis and develop novel therapeutic strategies for DTC.

Haplotype Based Analysis of XRCC3 Gene Polymorphisms in Thyroid Cancer

“…The present combined genotype frequency and their significance in thyroid carcinogenesis may show the synergistic effect of the selected polymorphisms on the said disease. So for only a few studies have been conducted regarding the combined genotypes of XRCC3 SNPs and their involvement in cancer, [59, 20] but the results are not comparable because they genotyped different SNPs.…”

DNA repair genes polymorphisms and genetic susceptibility to Philadelphia-negative myeloproliferative neoplasms in a Portuguese population: The role of base excision repair genes polymorphisms

“…Arg194Trp and Arg399Gln polymorphisms are among the most extensively studied SNPs in the XRCC1 gene (25,29,30,33–35,37,46,51, 53–55,59–63). These two SNPs have been shown to alter the functional activity of the resulting protein in vitro and to interfere with cancer susceptibility.…”

“…Previous reports have identified base excision repair (BER) genes polymorphisms associated with breast and thyroid cancer risk (33–35) among other malignancies, and a nucleotide excision repair gene polymorphism displayed strong association with leukaemic transformation and development of non-myeloid malignancies in patients with ET and PV (24). …”

Interaction Between XRCC1 Gene Polymorphisms and Obesity on Susceptibility to Papillary Thyroid Cancer in Chinese Han Population

“…Recently, two studies have reported associations of between XRCC1 and XRCC3 gene polymorphisms and risk of TC [11,12], but they concluded inconsistent results. In addition, increasing evidence suggests that combination of both genetic and environmental risk determinants contribute to the development and progression of PTC.…”