Qiao Yan, Ren Hua, Huang Ying, DU Zhong-li, Yu Dian-ke, Jin Jing, Li Ye-xiong, Lin Dong-xin, Tan Wen
Depatment of Etiology & Carcinogenesis, State Key Laboratory of Molecular Oncology, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Zhonghua Zhong Liu Za Zhi. 2013 Apr;35(4):268-72. doi: 10.3760/cma.j.issn.0253-3766.2013.04.006.
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).
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.
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.
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.
本研究旨在探讨接受以卡培他滨为基础的术后放化疗（CRT）的直肠癌患者中，细胞周期蛋白D1（CCND1）A870G单核苷酸多态性（SNP）与急性不良事件（AE）之间的关联。
本研究前瞻性纳入了400例接受含或不含奥沙利铂的卡培他滨术后CRT的II期和III期直肠癌患者。患者被随机分为两组。228例患者接受卡培他滨与放疗同步治疗（Cap-CRT），172例患者接受卡培他滨、奥沙利铂联合放疗（Cap-Oxa-CRT）。不良事件根据不良事件通用术语标准第3.0版（CTCAE v3.0）进行分级。通过基于聚合酶链反应的限制性片段长度多态性（PCR-RFLP）分析检测患者CCND1 A870G的基因型。SNP与急性AE之间的关联用比值比（OR）和95%置信区间（CI）表示，通过逻辑回归模型计算得出。
共有136例患者出现严重AE。其中，三种基因型GG、GA和AA的频率分别为16.9%、50.7%和32.4%，而未出现严重AE的患者中这三种基因型的频率分别为24.6%、48.1%和27.3%。腹泻是最常见的AE，109例患者出现严重腹泻。这些患者中三种基因型GG、GA和AA的频率分别为15.6%、47.7%和36.7%，而未出现严重腹泻的患者中这三种基因型的频率分别为24.4%、49.5%和26.1%。多因素逻辑回归分析显示，与GG或GA基因型患者相比，AA基因型患者发生严重腹泻的风险增加1.66倍（95%CI 1.03 - 2.67，P = 0.038）。分层分析显示，在Cap-Oxa-CRT组中，与GG或GA基因型患者相比，AA基因型患者发生严重腹泻的风险增加2.34倍（95%CI 1.16 - 4.76，P = 0.018），但在Cap-CRT组中，该SNP与严重腹泻风险无关。
CCND1 A870G的基因多态性可能是预测接受卡培他滨和奥沙利铂辅助同步放化疗的II期和III期直肠癌术后患者急性AE的潜在生物标志物。
