XPG遗传多态位点His46His和His1104Asp与卵巢癌患者铂类药物敏感性关系探讨

摘要

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％ CI 1.330～7.208).COX风险比例回归模型结果显示XPG遗传多态位点His46 His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 relationship between nucleotifie excision repair gene XPG munonucleotide polymorphism and the sensitivity to platinum-based chemotherapy in patients with ovarian cancer. Methods XPGHis46His and XPG HisllO4Asp were genotyped by PCR-RFLP DNA Sequencing method in the 102 patients with ovarian cancer with platinum-based chemotherapy, and the correlation of genetic polymorphisms and clinical chemotherapy response was analyzed. Results The polymorphism of Hisll04Asp was not significantly different between response group and un-re-sponse group(P>0. 05 ). The frequency of T/T,T/C and C/C genotypes in drug sensitivity group was significantly increased as compared with that in the drug resistant group(P =0. 016). Individuals carrying at least one 46C variant allele (T/C and C/C genotypes) tended to have an increased sensitivity (3. 096 times) to ovarian cancer patients with platinum-based chemotherapy as compared with those with the XPG46T/T genotype (95% CI 1. 330 ~ 7. 208). The COX risk regression model showed that the polymorphism of Hisl 104Asp and His46His was not an independent factor for prognosis of ovarian cancer( P < 0. 05). Conclusion Nucleotide excision repair gene XPGHis46His genetic polymorphism may be related to sensitivity to ovarian cancer patient' s platinum-based chemotherapy in ovarian cancer patients.