CAJ | 학술논문

目的探讨细胞周期素D1(CCND1)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CTCAE v3.0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CCND1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基因型的概率分布分别为24.4％、49.5％和26.1％.多因素分析结果表明,AA基因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,CCND1基因A870G多态与重度腹泻的发生无关.结论 CCND1 A870G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.
목적 탐토세포주기소D1(CCND1)기인단핵감산다태A870G여직장암술후동보방화료급성독부반응적관계.방법 수집Ⅱ～Ⅲ기직장암술후환자400례,진행전첨성림상수궤분조연구,기중228례환자접수잡배타빈단약동보방화료단약조,172례환자접수잡배타빈+오사리박쌍약동보방화료쌍약조.급성독부반응안조CTCAE v3.0표준진행분급.채용취합매련반응화한제성편단장도다태방법,분석직장암환자CCND1기인유전다태.채용Logistic회귀모형분석각기인형환자발생독부반응적풍험.결과 400례환자중,136례환자발생중도급성독부반응,GG、GA화AA기인형적빈솔분포분별위16.9％、50.7％화32.4％；재264례미발생중도급성독부반응적환자중,GG、GA화AA기인형적빈솔분포분별위24.6％、48.1％화27.3％.109례중도복사환자중,GG、GA화AA기인형적빈솔분포위15.6％、47.7％화36.7％；291례미발생중도복사환자중,GG、GA화AA기인형적개솔분포분별위24.4％、49.5％화26.1％.다인소분석결과표명,AA기인형환자발생중도복사적풍험시GG혹GA기인형환자적1.66배(95％ CI위1.03 ～ 2.67,P=0.038).재쌍약조중,AA기인형환자발생중도복사적풍험시GG혹GA기인형환자적2.34배(95％ CI위1.16 ～ 4.76,P=0.018)；이재단약조중,CCND1기인A870G다태여중도복사적발생무관.결론 CCND1 A870G다태가능시예측직장암술후잡배타빈+오사리박동보방화료급성독부반응적유전표지.
Objective The purpose of this study was to investigate the association between single nucleotide polymorphism (SNP) of CCND1 A870G and acute adverse events (AEs) in postoperative rectal cancer patients who received capecitabine-based postoperative chemoradiotherapy (CRT).Methods Four hundred patients with stage Ⅱ and Ⅲ rectal cancer received postoperative CRT of capecitabine with or without oxaliplatin were accumulated and prostectively 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-RFLP) analysis.The associations between the SNP and acute AEs were indicated by odds ratios (ORs) and 95％ confidence intervals (CIs),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 without severe 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 2.34-fold increased risk for severe diarrhea (95％ CI 1.16-4.76,P =0.018) compared with those with GG or GA genotypes,but in the Cap-CRT group,the SNP was not associated with the risk of severe diarrhea.Conclusions The genetic polymorphism of CCND1 A870G might be a potential biomarker for predicting acute AEs in postoperative stage Ⅱ and Ⅲ rectal cancer patients treated with adjuvant concurrent chemoradiotherapy of capecitabine and oxaliplatin.