ERCC1和XRCC1基因多态性与食管鳞癌发病及接受三维适形放疗疗效的关系

摘要

目的：探讨ERCC1和XRCC1基因多态性与食管鳞癌的发病风险及两者多态性与中晚期食管鳞癌三维适形放疗疗效的关系。方法收集218例食管鳞癌患者外周血样本作为疾病组，另选230例健康体检正常人群外周血样本作为对照组，采用PCR法扩增目的基因片段，直接测序法检测ERCC1、XRCC1的SNP 位点（ ERCCC1 rs3212986、ERCCC1 rs11615、XRCC1 rsl799782和XRCC1 rs25487），分析不同基因型和等位基因分布情况及其与食管鳞癌的患病风险，同时根据RECIST 1�1疗效评价标准将接受三维适形放疗的154例中晚期患者分为有效组（ CR＋PR）和无效组（ SD＋PD），分析以上SNP位点与中晚期食管鳞癌三维适形放疗疗效的关系。结果4个SNP位点的基因型分布均符合Hardy⁃Weinberg平衡。疾病组ERCC1 rs3212986、rs11615基因型和等位基因及XRCC1 rs25487等位基因的分布与对照组相比，差异均有统计学意义（ P＜0�05）。 ER⁃CC1 rs3212986、rs11615及XRCC1 rs25487中，以野生型纯合子为参照，突变型纯合子食管鳞癌风险均升高，且4种SNP位点中以野生型等位基因为参照，突变型等位基因食管鳞癌风险均升高，以上差异均有统计学意义（ P＜0�05）。154例仅放疗患者中，获CR者35例，PR者78例，SD 24例，PD 17例，故分为有效组113例和无效组41例。4种SNP位点不同基因型和等位基因治疗有效率的差异均有统计学意义（ P＜0�05）；以野生型纯合子为参照，突变型纯合子放疗无效的风险均升高，且以野生型等位基因为参照，突变型等位基因放疗无效的风险均升高，以上差异均有统计学意义（ P＜0�05）。结论 ERCC1和XRCC1基因多态性与食管鳞癌的发病风险相关，且中晚期患者中突变型纯合子和突变型等位基因的放疗无效风险均升高，故检测ERCC1和XRCC1基因多态性可能预测中晚期食管鳞癌三维适形放疗的疗效。%Objective To investigate the association between the risk of esophageal squamous cell carcinoma(ESCC) and polymorphisms in DNA repair genes ERCC1 and XRCC1 as well as the influence of polymorphisms on curative effect of three⁃dimen⁃sional conformal radiotherapy( 3D⁃CRT) for ESCC. Methods The peripheral blood samples from 218 ESCC patients were assigned as disease group and 230 cases of healthy normal people were assigned as control group. The PCR method was used to amplify the target gene fragment. The single nucleotide polymorphisms(SNP) of ERCC1 rs3212986, ERCC1 rs11615, XRCC1 rsl799782 and XRCC1 rs25487 were detected by direct sequencing. The distribution of different genotypes and alleles as well as their correlation with the risk of ESCC were analyzed. According to the RECIST 1�1, the 154 cases treated with 3D⁃CRT for advanced ESCC were divided into effec⁃tive group and ineffective group, and the relationship between the above SNP loci and curative effects of 3D⁃CRT for ESCC were further analyzed. Results The genotype distributions of the 4 SNP loci were consistent with the Hardy⁃Weinberg equilibrium in both groups. The distribution of ERCC1 rs3212986, ERCC1 rs11615 genotype and allele, and XRCC1 rs25487 allele in the disease group was sig⁃nificantly different from those of the control group( P<0�05) . When the wide homozygous of XRCC1 rs3212986, XRCC1 rs11615 and ERCC1 rs25487 were used as reference, the risk of mutant homozygous for ESCC was elevated. When the wide allele gene of 4 SNP lo⁃ci were used as reference, the risk of mutant allele for ESCC was higher( P<0�05) . Among 154 patients, 113 cases were divided into effective group(35 CR+78 PR) and 41 groups and the ineffective group(24 SD+17 PD). There were significant differences in the effi⁃ciency of different genotypes and allele of 4 SNP loci( P<0�05) . When the wide homozygous were used as reference, the risk of invalid radiotherapy in mutant homozygous was higher. The risk of the mutant allele genes for invalid radiotherapy was higher than that of the wide allele genes( P<0�05) . Conclusion ERCC1 and XRCC1 gene polymorphisms are associated with the risk of esophageal squa⁃mous cell carcinoma. The risk of invalid radiotherapy was elevated in advanced ESCC patients with mutate homozygous and allele genes.