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目的探讨核苷酸切除修复系统基因XPD遗传多态性与晚期结直肠癌(CRC)患者对铂类药物化疗敏感性的关系。方法对晚期CRC患者96例进行含奥沙利铂的联合化疗,以影像学方法判定其疗效。在治疗前抽血检测XPDAsp312Asn和XPDLys751Gln基因多态性,比较不同基因型患者的化疗敏感性。结果患者化疗后部分缓解(PR)20例,稳定(SD)59例,进展(PD)17例,有效率(RR)为20.8%。多因素分析表明,携带Gln/Gln基因型患者的疾病进展风险是至少携带一个Lys等位基因(Lys/Lys和Lys/Gln基因型)个体的7.8倍(OR=7.813,95%CI=1.834～33.277,P<0.05),但未观察到XPDAsp312Asn多态与化疗敏感性相关,未发现XPD基因多态在影响铂类药敏感性中存在联合作用。结论XPD基因遗传多态与晚期CRC对铂类化疗的敏感性相关。
Objective To investigate the relationship between XPD genetic polymorphisms of nucleotide excision repair system and chemosensitivity to platinum-based chemotherapy in patients with advanced colorectal cancer (CRC). Methods Ninety-six patients with advanced CRC were treated with oxaliplatin combined with chemotherapy, and their efficacy was evaluated by imaging method. Blood samples were collected before treatment to detect polymorphisms of XPDAsp312Asn and XPDLys751Gln, and to compare the chemosensitivity of different genotypes. Results After chemotherapy, there were 20 cases of partial remission (PR), 59 cases of stable (SD) and 17 cases of progressive (PD). The effective rate (RR) was 20.8%. Multivariate analysis showed that patients with Gln / Gln genotype had a risk of progression of at least 7.8-fold (OR = 7.813, 95% CI = 1.834 ~ 33.277, P <0.05). However, it was not observed that XPDAsp312Asn polymorphism was associated with chemosensitivity. No association of XPD polymorphism with platinum sensitivity was found. Conclusion The genetic polymorphism of XPD gene is associated with the sensitivity of advanced CRC to platinum chemotherapy.