MTHFR和ABCG2单核苷酸多态性对晚期结直肠癌一线化疗疗效的预测作用  

Predictive role of single nucleotide polymorphisms of MTHFR and ABCG2 genes in the response to first-line chemotherapy in advanced colorectal cancer

作　　者：赵静[1] 张文[1] 李文桦[1] 张哲[1] 朱丹[1] 余绮荷[1] 郭伟剑[1] 李进[1] 

机构地区：[1]复旦大学附属肿瘤医院肿瘤内科,复旦大学上海医学院肿瘤学系,上海200032

出　　处：《肿瘤》2012年第9期709-716,共8页Tumor

基　　金：上海市科学技术委员会科研计划项目(编号:09411967000)

摘　　要：目的:探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)和乳腺癌耐药蛋白(breast cancerr esistance protein,BCRP/ABCG2)基因单核苷酸多态性(sing lenucleotide polymorphism,SNP)对晚期结直肠癌一线化疗疗效的预测作用。方法:采用基因测序法检测154例接受FOLFOX、XELOX或FOLFIRI方案一线化疗的晚期结直肠癌患者外周血MTHFR677C>T、MTHFR1298A>C、ABCG234G>A和ABCG2421C>A这4个位点的SNP,结合临床特征,分析其与近期疗效、无进展生存(progression-free survival,PFS)和总生存(overall survival,OS)之间的关系。结果:154例患者接受一线化疗的有效率为31.8%,中位PFS为8.1个月,中位OS为30.7个月。MTHFR和ABCG2SNP与近期疗效和OS无显著相关性(P>0.05)。含3～4个优势基因型(MTHFR677C/C、MTHFR1298A/A、ABCG234G/A或A/A及ABCG2421C/A或A/A)患者的中位PFS较含0～2个优势基因型患者的显著延长(分别为9.8和7.5个月,P=0.013)。COX多因素分析结果显示,优势基因型数目(P=0.017)和原发灶是否根治切除(P=0.010)是影响PFS的独立因素。单因素和多因素分析结果均显示,原发灶是否根治切除是影响OS的独立因素(P=0.000,P=0.000)。结论:联合分析MTHFR和ABCG2SNP对一线化疗治疗晚期结直肠癌的PFS有一定的预测作用,原发灶是否根治切除是影响PFS和OS的独立因素。Objective： To investigate the predictive role of single nucleotide polymorphisms （SNPs） of methylenetetrahydrofolate reductase （MTHFR） and breast cancer resistance protein （BCRP/ABCG2） in the response to first-line chemotherapy in advanced colorectal cancer. Methods： The DNA sequencing technique was used to detect the SNPs of MTHFR 677C〉T, MTHFR 1298A〉C, MTHFR ABCG2 34G〉A and MTHFR 421C〉A in peripheral blood from 154 patients with advanced colorectal cancer receiving FOLFOX, XELOX or FOLFIRI regimen as first-line chemotherapy, and the relationships of SNPs with early response, progression-free survival （PFS） and overall survival （OS） were analyzed. Results： The overall response rate of first-line chemotherapy in 154 patients was 31.8%, and the median PFS and OS were 8.1 and 30.7 months, respectively. There was no significant correlation of MTHFR and ABCG2 SNPs with early response and OS （P 〉 0.05）. Patients carrying 3-4 favorable genotypes （MTHFR 677C/C, MTHFR 1298A/A, ABCG2 34G/A or A/A and ABCG2 421C/A or A/A） had a longer median PFS than those carrying 0-2 favorable genotypes （9.8 vs 7.5 months, P = 0.013）. COX multivariate analysis revealed that the factors of number of favorable genotypes （P = 0.017） and radical resection of primary lesion （P = 0.010） were independent factors for PFS. Both univariate and multivariate analyses showed that OS was independently associated with radical resection of primary lesion （both P ﹦ 0.000）. Conclusion： Combined detection of MTHFR and ABCG2 SNPs may play a role in predicting PFS of patients with advanced colorectal cancer receiving first-line chemotherapy. Radical resection of primary lesion is an independent prognostic factor for both PFS and OS.

关 键 词：结直肠肿瘤 药物疗法 多态性 单核苷酸 预测 亚甲基四氢叶酸还原酶 乳腺癌耐药蛋白 

分 类 号：R730.53[医药卫生—肿瘤]