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目的探讨核苷酸切除修复基因XPG单核苷酸多态性与卵巢癌患者对铂类药物敏感性的关系。方法 2002年6月至2009年6月在广西医科大学附属肿瘤医院以聚合酶链-限制性片段长度多态性(PCR-RFLP)和DNA序列测定方法检测接受含铂类药物化疗的102例卵巢上皮细胞癌患者的XPGHis46His及XPGHis1104Asp的多态基因型,并比较不同基因型与化疗敏感性的关系。结果 His1104Asp多态性在卵巢癌铂类药物化疗敏感组中分布与耐药组差异无统计学意义(P>0.05)。而XPGHis46His在化疗敏感组T/T,T/C,C/C的基因型频率明显高于耐药组(P=0.016),与携带XPG46T/T基因型比较,携带至少一个46C等位基因(即T/C和C/C基因型)的卵巢癌患者对铂类药物化疗敏感性增加3.096倍(95%CI1.330~7.208)。COX风险比例回归模型结果显示XPG遗传多态位点His46His和His1104Asp不是卵巢上皮癌患者的独立预后因素(P<0.05)。结论核苷酸切除修复系统中XPGHis46His遗传多态可能与卵巢癌患者对铂类药物敏感性相关。
Objective To investigate the association of single nucleotide polymorphisms of nucleotide excision repair gene XPG with platinum-based drugs in patients with ovarian cancer. Methods From June 2002 to June 2009, 102 ovarian cancer patients receiving platinum-containing chemotherapy were detected by polymerase chain-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing in the Tumor Hospital of Guangxi Medical University. The genotypes of XPGHis46His and XPGHis1104Asp in patients with epithelial cell carcinoma were compared, and the relationship between different genotypes and chemosensitivity was compared. Results His1104Asp polymorphism in the ovarian cancer platinum-sensitive chemotherapy group distribution and drug resistance was no significant difference (P> 0.05). However, the genotype frequency of XPGHis46His in chemosensitive group was significantly higher than that in drug resistant group (P = 0.016). Compared with XPG46T / T genotype, XPGHis46His carried at least one 46C allele (T / C and C / C genotypes) were 3.096-fold (95% CI, 1.330 to 7.208) higher in response to platinum-based chemotherapies. COX risk proportional regression model results showed that XPG genetic polymorphisms His46His and His1104Asp are not independent prognostic factors in patients with epithelial ovarian cancer (P <0.05). Conclusion XPGHis46His polymorphism in the nucleotide excision repair system may be related to the sensitivity of ovarian cancer patients to platinum drugs.