Background: Base excision repair (BER) plays an important role in the maintenance of genome integrity and anticancer drug resistance. This study aimed to explore the role of BER gene polymorphisms in response to chemotherapy for advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy.
Methods: During the period from November 2009 to January 2016, a total of 152 patients diagnosed with NSCLC Stage IIIB and IV in the First Hospital of Jilin University were admitted into this study. The XRCC1 G28152A, MUTYH G972C, HOGG1 C1245G, and PARP1 T2444C polymorphisms of all the patients were detected by mass spectrometry. The logistic regression was used for statictical analysis. All tests were bilateral test, and a P < 0.05 was considered statistically significant.
Results: The logistic regression model showed that the response rate of chemotherapy of the PARP1 T2444C polymorphisms, CC genotype (odds ratio [OR]: 5.216, 95% confidence interval [CI]: 1.568-17.352, P = 0.007), TC genotype (OR: 2.692, 95% CI: 1.007-7.198, P = 0.048), as well as the genotype of TC together with CC (OR: 3.178, 95% CI: 1.229-8.219, P = 0.017) were significantly higher than those of TT wild type. There was no relationship between the MUTYH G972C, XRCC1 G28152A, and HOGG1 C1245G gene polymorphisms and chemosensitivity.
Conclusions: The PARP1 2444 mutation allele C might be associated with the decreased sensitivity to platinum-based chemotherapy in advanced NSCLC. These findings may be helpful in designing individualized cancer treatment.
碱基切除修复基因多态性与晚期非小细胞肺癌化疗疗效的关系摘要目的：碱基切除修复通路(BER)在维持基因完整性和抗肿瘤耐药性中起着重要作用。本研究旨在探讨BER基因多态性与铂类治疗晚期非小细胞肺癌(NSCLC)疗效的关系。 方法：收集 2009 年 11 月~2016 年 1 月，在吉林大学第一医院收治并经病理学确诊的IIIB 或IV 期符合研究标准的 152 例非小细胞肺癌(NSCLC)患者。采用质谱法检测XRCC1 G28152A、MUTYH G972C、HOGG1 C1245G及PARP1 T2444C基因多态性，对测定结果通过 logistic 回归模型进行统计学分析。 结果：Logistic 回归模型示PARP1 T2444C的CC基因型化疗有效率显著高于TT野生型(OR:5.216， 95%CI: 1.568-17.352，P =0.007);TC基因型化疗有效率高于TT野生型 (OR: 2.692，95%CI: 1.007-7.198，P =0.048);携带TC基因型或CC基因型的患者的化疗有效率高于 TT 基因型患者(OR:3.178，95%CI: 1.229-8.219，P = 0.017)。XRCC1 G28152A、MUTYH G972C及HOGG1 C1245G基因多态性与化疗敏感性之间均未发现显著相关性。 结论：携带PARP1 2444 位点的等位基因C可能与铂类联合方案治疗晚期非小细胞肺癌的敏感性降低有关。我们的研究结果可能有助于指导肿瘤的个体化治疗。.
Keywords: Base Excision Repair; Chemotherapy; DNA Repair; Genetic; Non-Small Cell Lung Cancer; Platinum; Polymorphism.