Zhou Qiang, Zou Bing-Wen, Xu Yong, Xue Jian-Xin, Meng Mao-Bin, Liu Fang-Jiu, Deng Lei, Ma Dai-Yuan, Ao Rui, Lu You
Department of Thoracic Oncology, Cancer Center and State Key Laboratory, West China Hospital, Medical School, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, People's Republic of China.
Tumour Biol. 2015 Mar;36(3):1539-48. doi: 10.1007/s13277-014-2718-y. Epub 2014 Nov 6.
Polymorphisms in DNA repair genes impact on the synthesis of DNA repair proteins that are crucial to the repair of DNA damages induced by chemotherapy and radiotherapy. We retrospectively examined whether there was an association between the selected six single nucleotide polymorphisms (SNPs) of five DNA repair genes (PARP1-Val762Ala, XRCC1-Arg194Trp, XRCC1-Arg399Gln, XPC-Lys939Gln, BRCA1-Lys1183Arg, and BRCA2-Asn372His) and the clinical outcome of patients with primary small cell carcinoma of esophagus (SCCE), and it showed that the median progression-free survival (PFS) and the overall survival (OS) were 11.8 versus 9.7 months (P = 0.041) and 17.4 versus 14.8 months (P = 0.032) for patients carrying the variant allele (T/C + C/C) and the wild-type allele (T/T) of PARP1-Val762Ala polymorphism, respectively. However, no statistical significance was observed in the other five polymorphic loci (P > 0.05). When these six SNPs were combined, however, patients with at least three variant genotypes had significantly longer PFS and OS compared with those carrying less than three variant genotypes (P = 0.009 and P = 0.007, respectively). The presence of at least three polymorphic variants in certain DNA repair genes may impact on patient survival and could be a potential genomic predictor of clinical response to DNA-damaging treatment in SCCE patients.
DNA修复基因中的多态性会影响DNA修复蛋白的合成，而这些蛋白对于修复化疗和放疗诱导的DNA损伤至关重要。我们回顾性研究了五个DNA修复基因（PARP1-Val762Ala、XRCC1-Arg194Trp、XRCC1-Arg399Gln、XPC-Lys939Gln、BRCA1-Lys1183Arg和BRCA2-Asn372His）中选定的六个单核苷酸多态性（SNP）与原发性食管小细胞癌（SCCE）患者临床结局之间的关联，结果显示，对于携带PARP1-Val762Ala多态性变异等位基因（T/C + C/C）和野生型等位基因（T/T）的患者，中位无进展生存期（PFS）分别为11.8个月和9.7个月（P = 0.041），总生存期（OS）分别为17.4个月和14.8个月（P = 0.032）。然而，在其他五个多态性位点未观察到统计学意义（P > 0.05）。然而将这六个SNP合并分析时，具有至少三种变异基因型的患者与携带少于三种变异基因型的患者相比，PFS和OS显著更长（分别为P = 0.009和P = 0.007）。某些DNA修复基因中至少存在三种多态性变异可能会影响患者生存，并且可能是SCCE患者对DNA损伤治疗临床反应的潜在基因组预测指标。
