ERCC5基因+25A＞G多态性与晚期结直肠癌铂类药物疗效的相关性

摘要

目的 探讨切除修复交叉互补基因5(ERCC5)基因单核苷酸多态性与中国汉族晚期结直肠癌患者铂类药物疗效的相关性.方法 应用PCR-LDR法检测以奥沙利铂为主化疗的105例晚期结直肠癌患者ERCC5基因位点+25A＞G (rs751402)、+202C＞T (rs2296147)及+372C＞T (rs2296148)的多态性,分析不同基因型与疾病控制率、无进展生存期(PFS)的相关性.结果 本研究人群中各多态性位点的基因型分布均符合Hardy-Weinberg平衡.携带+25A等位基因(AA/AG基因型) 患者经以奥沙利铂为主化疗的疾病控制率为73.5%,显著高于携带+25GG基因型患者的51.4%(χ2=5.231,P=0.022).携带+25GG基因型患者的中位PFS为5个月,低于携带+25AG基因型患者的8个月以及+25AA基因型患者的6个月(χ2=6.916,P=0.009).+202C＞T、+372C＞T位点多态性与疾病控制率、中位PFS之间均无显著差异.结论 晚期结直肠癌ERCC5基因+25A＞G单核苷酸多态性与奥沙利铂化疗的临床疗效相关.%Objective To study the relationship between single nucleotide polymorphisms (SNP) in the ERCC5(excision repair cross complementation group 5 ) gene and clinical outcome of Chinese patients with advanced colorectal cancer treated with oxaliplatin-based chemotherapy. Methods Polymorphisms of + 25A ＞ G ( rs7551402 ), + 202C ＞ T ( rs2296147 ) and + 372C ＞ T (rs2296148) in the ERCC5 gene were detected by PCR-LDR (polymerase chain reaction-ligation detection reaction) from 105 advanced colorectal cancer patients treated with oxaliplatin-besed chemotherapy. Statistical analysis was conducted to investigate the association between gene polymorphisms and clinical outcome. Results The genotype distribution of each polymorphism was found to be of Hardy-Weinberg equilibrium in the study. The disease control rate of patients with + 25A allele (73. 5％ ) was significantly higher than that of those with + 25GG genotype (X2 = 5. 231, P = 0. 022 ). No significant association or trend was found between + 202C ＞ T, + 372C ＞T polymorphism and disease control rate. The median progression free survival (PFS) of patients with the +25GG genotype ( 35/95 cases, 5 months ) was significantly lower than that of patients with other genotypes (48/95 case, 8 months for + 25AG genotype and 12/95 cases, 6 months for + 25 AA genotype, X2 = 6. 916, P = 0. 009 ). No significant difference was found between genotypes of + 202C ＞ T or + 372C ＞ T in the study. Conclusion The results suggested that ERCC5 + 25 A ＞ G polymorphism may be associated with clinical outcome of oxaliplatin-based chemotherapy in Chinese patients with advanced coiorectal cancer.