Yan Li, Li Qinghuai, Li Xiaoyu, Ji Hong, Zhang Linlei
Cell Physiol Biochem. 2016;38(3):1075-84. doi: 10.1159/000443058. Epub 2016 Mar 4.
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.
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).
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).
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.
背景/目的：DNA同源重组修复（HRR）途径和碱基切除修复（BER）途径在分化型甲状腺癌（DTC）的发展中起着至关重要的作用，因此我们推测XRCC1、XRCC2、XRCC3 DNA修复基因的多态性与甲状腺癌的风险及进展相关。
我们在NCBI数据库中搜索相关文献，以确定纳入本研究的8个单核苷酸多态性（SNP）（XRCC1：rs25487、rs25489、rs1799782；XRCC2：rs3218536；XRCC3：rs1799794、rs56377012、rs1799796、rs861539）。
rs25487的SNP与DTC风险降低53%相关（比值比：0.47；95%置信区间：0.268 - 0.82；P = 0.01）。对于rs1799782的SNP，纯合子TT基因型在多因素调整后显示DTC风险有统计学意义的2倍增加（比值比：2.09；95%置信区间：1.27 - 3.43；P < 0.001）。对于rs861539的SNP，纯合子TT基因型提示DTC风险有统计学意义的3倍增加（比值比：3.02；95%置信区间：1.68 - 5.42；P < 0.001）。其他5个SNP与DTC风险之间无显著关联。除此之外，在多因素调整后，女性与DTC风险增加47%相关（比值比：1.47；95%置信区间：1.062 - 2.04；P = 0.02）。通过不同组织学类型的DTC进行亚组分析，获得了大多数SNP的类似结果。单倍型分析显示XRCC1多态性的AGC和GGT单倍型与DTC相关。此外，基因 - 基因相互作用的结果表明，XRCC1 - rs25487、XRCC1 - rs1799782和XRCC3 - rs861539变异共同导致DTC风险特别增加，rs1799782 - CT杂合子和rs861539 - TT纯合子的联合变异显示出更高的3.66倍DTC风险（比值比：3.66；95%置信区间：1.476 - 9.091，P = 0.005）。
XRCC1（rs25487、rs1799782）和XRCC3（rs861539）的多态性可能在DTC的发生和发展中起关键作用。此外，XRCC1变异可与XRCC3变异相互作用，显著增加DTC易感性。识别这些遗传风险标志物可为探索DTC的发病机制和开发新的治疗策略提供依据。
