PARP1单核苷酸多态性对晚期胃癌奥沙利铂化疗反应及预后的影响

Impacts of PARP1 single nucleotide polymorphism on response to oxaliplatin-based chemotherapy and prognosis of advanced gastric cancer

目的探讨多聚腺苷二磷酸核糖聚合酶(PARP-1)单核苷酸多态性(SNP)与晚期胃癌患者化疗反应及生存时间的关联性。方法选择2016年5月至2019年12月于苏州科技城医院肿瘤内科收治的161例晚期胃癌患者,给予奥沙利铂联合替吉奥化疗,化疗前抽空腹静脉血5 ml用于提取基因组DNA。TaqMan探针法鉴别PARP1基因rs907187C/G、rs1805414T/C和rs1136410T/C多态性位点的基因型,分析各多态性对化疗客观反应率(ORR)及总生存期(OS)的影响。结果rs907187C/G多态性与化疗敏感性存在明显关联,变异等位基因G携带者化疗ORR显著升高,CC、CG、GG基因型分别为23.2%、42.2%、53.7%(P=0.007)。杂合基因型CG化疗ORR为CC基因型的2.362倍(P=0.035);纯合变异基因型GG化疗ORR为CC基因型的3.812倍(P=0.003);CG+GG基因型化疗ORR为CC基因型的2.854倍(P=0.005)。Kaplan-Meier分析显示rs1136410T/C多态性与患者OS显著相关,变异等位基因C携带者中位OS明显延长,TT、TC、CC基因型分别为10.0、13.1、16.9个月(P=0.006);TC+CC基因型患者中位OS为14.5个月,较TT组OS显著延长(P=0.004)。Cox比例风险模型分析显示,rs1136410T/C多态性仍是晚期胃癌患者OS的独立影响因素(P=0.010,OR=1.667,95%CI:1.131~2.458)。未发现rs1805414T/C多态性与化疗ORR及预后之间存在统计学关联。结论PARP1基因rs907187C/G多态性能影响晚期胃癌患者的ORR,而rs1136410T/C多态性可能是评估生存时间的预测指标。

Objective To investigate the associations of single nucleotide polymorphism(SNP)in poly-adenosine diphosphate-ribose polymerase(PARP)-1 gene with chemotherapy response and survival time in patients with advanced gastric cancer.Methods From May 2016 to December 2019,161 patients with advanced gastric cancer in Suzhou Science and Technology Town Hospital were treated with oxaliplatin and teggio chemotherapy.Before treatment,5 ml of fasting venous blood was drawn to extract genomic DNA in all patients.TaqMan probe was used to identify the genotypes of rs907187C/G,rs1805414T/C and rs1136410T/C polymorphic loci of PARP1 gene,and the influences of these polymorphisms on objective response rate(ORR)and overall survival(OS)were analyzed.Results The rs907187C/G polymorphism was significantly associated with chemotherapy sensitivity.The ORR to chemotherapy was significantly higher in the carriers of G variant allele,and CC,CG and GG genotypes were 23.2%,42.2%and 53.7%respectively(P=0.007).The ORR to chemotherapy of heterozygous CG genotype was 2.362 times that of CC genotype(P=0.035).The ORR of variant homozygous GG genotype was 3.812 times that of CC genotype(P=0.003).The ORR of CG and GG genotype was 2.854 times that of CC genotype(P=0.005).Kaplan-Meier analysis showed that rs1136410T/C polymorphism was significantly associated with OS;the median OS of the carriers of C variant allele was significantly prolonged and were 10.0,13.1 and 16.9 months,respectively in TT,TC and CC genotype(P=0.006);the median OS of TC and CC genotype was 14.5 months and was significantly longer than that of TT genotype(P=0.004).Cox proportional hazards model analysis showed that rs1136410T/C polymorphism was an independent influencing factor of OS in patients with advanced gastric cancer(P=0.010,OR=1.667,95%CI:1.131-2.458).No significant associations of rs1805414T/C polymorphism with ORR to chemotherapy and prognosis were found.Conclusion The rs907187C/G polymorphism of PARP1 gene can affect the ORR of chemotherapy,and rs1136410T/C polymorphism may be a predictor of survival time in patients with advanced gastric cancer.