BRCA1基因多态性与转移性食管鳞癌顺铂联合卡培他滨化疗敏感性及预后关系

目的：研究乳腺癌易感基因1(breast cancer susceptibility gene1，BRCA1)单核苷酸多态性(single nucleotide polymorphism，SNP)对转移性食管鳞癌患者化疗敏感性及生存预后的影响。方法：选取2016年6月至2020年2月于苏州科技城医院收治的153例初治转移性食管鳞癌患者，均给予顺铂联合卡培他滨化疗。首次化疗前抽静脉血5ml提取DNA，应用TaqMan探针法检测BRCA1基因rs8176318G/T 、rs799917T/C和rs1799966T/C多态性位点的基因型，探讨不同基因型之间化疗客观反应率 (objective response rate，RR)和总生存期(overall survival，OS)的差异。结果：rs799917T/C多态性与转移性食管鳞癌化疗敏感性密切相关，TT、TC、CC基因型化疗有效率呈逐渐升高趋势(TT 22.5%、TC 38.6%、CC 55.3%，χ2=8.041，P=0.018)。CC基因型化疗反应率为TT基因型的4.154倍 (95%CI：1.549~11.141，χ2=8.007，P=0.005)；TC+CC基因型化疗反应率为TT基因型的2.678倍 (95%CI：1.160~6.179，χ2=5.329，P=0.021)。Kaplan-Meier分析显示rs1799966T/C多态性与患者生存时间相关， TT、TC和CC基因型携带者中位OS呈逐渐延长趋势 (TT8.5月、TC12.1月、CC13.8月，χ2=11.864，P=0.003)； TC+CC基因型患者中位OS为12.6个月，与TT组相比明显延长(χ2=10.515，P=0.001)。COX回归模型分析结果显示，rs1799966T/C多态性仍是影响患者OS的独立预后因素。未发现rs8176318G/T多态性与化疗反应及预后之间存在统计学关联。结论：BRCA1基因rs799917多态性与转移性食管鳞癌顺铂联合卡培他滨化疗敏感性相关，rs1799966多态性可能影响患者的生存预后。

Correlation of BRCA1 gene polymorphism with chemosensitivity and prognosis of metastatic esophageal squamous cell carcinoma treated with cisplatin combined with capecitabine

AIM: To explore the effect of single nucleotide polymorphism (SNP) of breast cancer susceptibility gene 1 (BRCA1) on chemotherapy sensitivity and survival prognosis of patients with metastatic esophageal squamous cell carcinoma. METHODS: A total of 153 patients with newly treated metastatic esophageal squamous cell carcinoma who were admitted to Suzhou Science and Technology City Hospital from June 2016 to February 2020 were included and administered with cisplatin combined with capecitabine chemotherapy. Before the first chemotherapy, 5 mL of venous blood was collected to extract DNA, and the TaqMan probe method was used to detect the genotypes of the BRCA1 gene rs8176318G/T, rs799917T/C and rs1799966T/C polymorphic loci. The objective response rate (ORR) and overall survival (OS) of different genotypes were analyzed. RESULTS: Rs799917T/C polymorphism was closely related to the chemosensitivity of metastatic esophageal squamous cell carcinoma. The chemotherapy response rates of TT, TC and CC genotypes increased gradually (TT 22.5%, TC 38.6%, CC 55.3%, χ2 = 8.041, P=0.018). The chemotherapy response rate of the CC genotype was 4.154 times that of the TT genotype (95%CI: 1.549 11.141, χ2=8.007, P=0.005); the chemotherapy response rate of the TC+CC genotype was 2.678 times that of the TT genotype (95%CI: 1.160 6.179, χ2=5.329, P=0.021). Kaplan Meier analysis showed that the rs1799966T/C polymorphism was related to the survival time of patients, and the median OS of carriers of TT, TC and CC genotypes showed a gradually prolonging trend (TT 8.5 months, TC 12.1 months, CC 13.8 months, χ2 =11.864, P=0.003); The median OS of patients with TC+CC genotype was 12.6 months, which was significantly longer than that in the TT group (χ2=10.515, P=0.001). COX regression model analysis showed that the polymorphism of rs1799966T/C was still an independent prognostic factor of OS. There was no statistical correlation between rs8176318G/T polymorphism, chemotherapy response and prognosis. CONCLUSION: The rs799917 polymorphism of BRCA1 gene is associated with the sensitivity of cisplatin combined with capecitabine in metastatic esophageal squamous cell carcinoma, and rs1799966 polymorphism may affect the prognosis of patients.