XRCC1基因多态性与FOLFOX方案治疗胃肠癌敏感性的关系  

Relationship between genetic polymorphisms of XRCC1 and chemosensitivity of gastrointestinal cancer to FOLFOX chemotherapy

作　　者：任晓华[1] 邬晓敏[2] 崔永安[2] 

机构地区：[1]扬州市妇幼保健院,江苏扬州225002 [2]扬州大学医学院,江苏扬州225001

出　　处：《现代肿瘤医学》2010年第4期741-745,共5页Journal of Modern Oncology

基　　金：扬州大学自然科学基金项目(编号:2006XJJ16)

摘　　要：目的:探索DNA损伤基因XRCC1G28152A(Arg399G1n)多态性与接受奥沙利铂为基础FOLFOX方案治疗晚期胃肠癌患者药物有效率、中位TTP和不良反应间的关系。方法:48例(其中可观察有效率组22例)胃肠癌患者抽取外周血并提取DNA,以PCR-RFLP等方法检测XRCC1G28152A(Arg399G1n)位点多态性,观察化疗期间患者不良反应,有效率及中位TTP。比较不同基因型与有效率、中位TTP、不良反应间的关系。结果:XRCC1G28152A(Arg399G1n)在22例可观察有效率组患者中,G/G、G/A基因频度分别为50%(11例)、50%(11例),有效率分别为72.7%、27.3%,差异有显著性(P=0.033)。48例患者中G/G、G/A、A/A基因频度分别为52.1%(25例)、45.8%(22例)、2.1%(1例),G/G、G/A+A/A的中位TTP分别为9.0个月、5.0个月,差异有显著性(P=0.01)。48例患者中,G/G、G/A+A/A基因型恶心呕吐分别为44%、79.2%,差异有显著性(P=0.015)。G/G、G/A+A/A间骨髓抑制、静脉炎、外周神经毒性、肝毒性、腹泻差异无显著性(P>0.05)。结论:XRCC1 G28152A(Arg399G1n)多态位点与晚期胃肠癌接受奥沙利铂为基础FOLFOX方案一线治疗的有效率、中位进展期及恶心呕吐发生率有关。Objective：To investigate the relationship between the polymorphism in DNA damage-related gene,XRCC1G28152A（Arg399G1n）,and the clinical therapeutic effects of a therapeutic regimen based on oxaliplatin designated as FOLFOX（Oxaliplatin ＋ CF ＋ 5-Fu） on advanced gastrointestinal cancer.Methods：Total of 48 patients with advanced gastrointestinal cancer were ovserved and 22 of them were included in the group evaluated for general effective rate.Genomic DNA was extracted from peripheral venous blood and the polymorphism in candidate gene was studied by PCR-RFLP analysis.Relationships between different genotypes and toxic side effects,general effective rate and median time to progression（TTP） were studied during the chemotherapeutic period.Results：In 22 cases evaluated for general effective rate,the genotypic frequencies for G/G and G/A were both 50%.Individuals inheriting different genotypes at this locus had significant difference in general effective rate,72.7% and 27.3% for G/G and G/A,respectively（P=0.033）.In the whole 48 tested patients,the genotypic frequencies for G/G,G/A and A/A were 52.1%（25 cases）,45.8%（22 cases） and 2.1%（1 case）,respectively.Individuals inheriting the homozygous G/G genotype at this polymorphic site had a significantly higher TTP value（9.0 months,P=0.01） and a much lower occurring rate of nausea and vomiting（44%,P=0.015）.As for individuals inheriting the A allele（G/A and A/A genotypes）,the TTP value was 5.0 months and the occurring rate of nausea and vomiting was 79.2%.No significant difference was detected in other traits we measured,such as marrow inhibition,phlebitis,peripheral neurotoxicity,hepatotoxicity,and diarrhea（P〉0.05）.Conclusion：Different genotypes at G28152A locus in XRCC1 was closely related to the effective rate and TTP value in the patients with advanced gastrointestinal cancer treated with FOLFOX regimen.

关 键 词：胃肠癌 基因多态性 奥沙利铂 FOLFOX XRCC1 

分 类 号：R730.3[医药卫生—肿瘤] R735.34[医药卫生—临床医学]