细胞周期素D1基因A870G多态与直肠癌术后同步放化疗急性毒副反应的关系  

Impact of CCND1 A870G polymorphism on acute adverse events in postoperative rectal cancerpatients treated with adjuvant concurrent chemoradiotherapy

作　　者：乔艳[1,2,3] 任骅 黄莹[1,2,3] 杜忠礼 于典科[1,2,3] 金晶 李晔雄 林东昕[1,2,3] 谭文[1,2,3] 

机构地区：[1]中国医学科学院北京协和医学院肿瘤医院肿瘤研究所病因及癌变研究室 [2]分子肿瘤学国家重点实验室 [3]癌发生及预防分子机理北京市重点实验室 [4]放疗科

出　　处：《中华肿瘤杂志》2013年第4期268-272,共5页Chinese Journal of Oncology

基　　金：北京市科技计划项目（D0905001040531）

摘　　要：目的探讨细胞周期素D1（CCNDl）基因单核苷酸多态A870G与直肠癌术后同步放化疗急性毒副反应的关系。方法收集Ⅱ～Ⅲ期直肠癌术后患者400例，进行前瞻性临床随机分组研究，其中228例患者接受卡培他滨单药同步放化疗单药组，172例患者接受卡培他滨＋奥沙利铂双药同步放化疗双药组。急性毒副反应按照CTCAEv3．0标准进行分级。采用聚合酶链反应和限制性片段长度多态方法，分析直肠癌患者CCNDl基因遗传多态。采用Logistic回归模型分析各基因型患者发生毒副反应的风险。结果400例患者中，136例患者发生重度急性毒副反应，GG、GA和AA基因型的频率分布分别为16．9％、50．7％和32．4％；在264例未发生重度急性毒副反应的患者中，GG、GA和AA基因型的频率分布分别为24．6％、48．1％和27．3％。109例重度腹泻患者中，GG、GA和AA基因型的频率分布为15．6％、47．7％和36．7％；291例未发生重度腹泻患者中，GG、GA和AA基因璎的概率分布分别为24．4％、49．5％和26．1％。多因素分析结果表明，AA基[天J型患者发生重度腹泻的风险是GG或GA基因型患者的1．66倍（95％CI为1．03～2．67，P=0．038）。在双药组中，AA基因型患者发生重度腹泻的风险是GG或GA基因型患者的2．34倍（95％CI为1．16～4．76，P=0．018）；而在单药组中，CCNDl基因A870G多态与重度腹泻的发生无关。结论CCNDlA870G多态可能是预测直肠癌术后卡培他滨＋奥沙利铂同步放化疗急性毒副反应的遗传标志。Objective The purpose of this study was to investigate the association between single nucleotide polymorphism （SNP） of CCND1 ABTOG and acute adverse events （AEs） in postoperative rectal cancer patients who received capecitabine-based postoperative ehemoradiotherapy （CRT）. Methods Four hundred patients with stage II and I]I rectal cancer received postoperative CRT of capeeitabine with or without oxaliplatin were accumulated and prosteetively studied in this study. The patients were randomly divided into two groups. Two hundred and twenty-eight patients were treated with concurrent capecitabine and radiotherapy （Cap-CRT）, and 172 patients were treated with capecitabine and oxaliplatin plus radiotherapy （Cap-Oxa-CRT）. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, v. 3.0 （CTCAE v3.0）. The genotype of CCND1 A870G in the patients was detected by polymerase chain reaction-based restriction fragment length polymorphism （PCR-RELP） analysis. The associations between the SNP and acute AEs were indicated by odds ratios （ORs） and 95% confidence intervals （Cls）, which were computed with logistic regression model. Results A total of 136 patients presented severe AEs. Among them the frequencies of the three genotypes GG, GA and AA were 16.9%, 50.7% and 32.4% , compared with 24.6% , 48.1% and 27.3% , respectively, among the patients withoutsevere AEs. Diarrhea was the most common AE, and severe diarrhea occurred in 109 patients. The frequencies of the three genotypes GG, GA and AA were 15.6% , 47.7% and 36.7% among these patients, compared with 24.4%, 49.5% and 26.1%, respectively, among patients without severe diarrhea. Multivariate logistic regression analysis showed a 1.66-fold increased risk for severe diarrhea in patients with AA genotype （95% CI 1.03-2.67, P =0. 038） compared with the cases with GG or GA genotypes. Stratified analysis showed that in the Cap-Oxa-CRT group, patients with AA genotype showed a 2.3d-fold increased risk for seve

关 键 词：直肠肿瘤 多态性 单核苷酸 细胞周期素D1 同步放化疗 毒副反应 

分 类 号：R735[医药卫生—肿瘤]