Shen Xiaobing, Wang Jia, Yan Xiaoluan, Ren Xiaofeng, Wang Fan, Chen Xiaowei, Xu Yuchao
School of Public Health, Southeast University, No. 87, Dingjiaqiao Road, Nanjing, 21000, China.
Cancer Chemother Pharmacol. 2016 Jun;77(6):1285-302. doi: 10.1007/s00280-016-3047-1. Epub 2016 May 6.
Gastric and colorectal cancers remain the major causes of cancer-related death with a bad prognosis. Up to now, platinum combined with fluoropyrimidines has been most commonly used in chemotherapy regimens of gastric and colorectal cancers. Recently, a series of studies have been conducted to investigate the associations of biomarkers, such as GSTP1 Ile105Val polymorphism, with the chemotherapy efficacy in gastric and colorectal cancers; however, the results were not consistent and inconclusive. Here, we performed a systematic review and meta-analysis to summarize the associations of GSTP1 Ile105Val polymorphism with the chemotherapy efficacy in gastric and colorectal cancers.
A systematic review was conducted to search relevant studies in English databases (PubMed, ISI Web of Science, and EMBASE) up to November 30, 2015. The pooling ORs or HRs were used to assess the strength of the associations of GSTP1 Ile105Val polymorphism with clinical outcomes such as tumor response, toxicity, progression-free survival (PFS), and overall survival (OS).
Forty-one papers containing 8169 cases were finally included in the present meta-analysis study. Of which, 28 articles were performed in colorectal cancers, one in gastrointestinal carcinoma (gastric and colon cancer), 11 in gastric cancers, and one in colorectal and gastroesophageal cancers. After pooling all the eligible studies, we identified significant associations of GSTP1 Ile105Val polymorphism with chemotherapy-related tumor response (G vs. A: OR 1.697, 95 % CI 1.191-2.418; GG vs. AA: OR 2.804, 95 % CI 1.414-5.560; AG vs. AA: OR 1.540, 95 % CI 1.011-2.347; GG vs. AAAG: OR 2.139, 95 % CI 1.256-3.641), PFS (GG vs. AA, HR 0.640, 95 % CI 0.455-0.900; AGGG vs. AA: HR 0.718, 95 % CI 0.562-0.919), and OS (AG vs. AA: HR 0.857, 95 % CI 0.746-0.986; GG vs. AA: HR 0.679, 95 % CI 0.523-0.882; AGGG vs. AA: HR 0.663, 95 % CI 0.542-0.812) in gastric and colorectal cancers and no significant association was found between the polymorphism with toxicity.
GSTP1 Ile105Val polymorphism was associated with tumor response, PFS, and OS in gastric and colorectal cancers after chemotherapy.
胃癌和结直肠癌仍然是癌症相关死亡的主要原因，预后较差。到目前为止，铂类联合氟嘧啶一直是胃癌和结直肠癌化疗方案中最常用的药物。最近，已经开展了一系列研究来调查生物标志物（如GSTP1 Ile105Val多态性）与胃癌和结直肠癌化疗疗效之间的关联；然而，结果并不一致且尚无定论。在此，我们进行了一项系统评价和荟萃分析，以总结GSTP1 Ile105Val多态性与胃癌和结直肠癌化疗疗效之间的关联。
进行系统评价，以检索截至2015年11月30日英文数据库（PubMed、ISI Web of Science和EMBASE）中的相关研究。合并的比值比（OR）或风险比（HR）用于评估GSTP1 Ile105Val多态性与临床结局（如肿瘤反应、毒性、无进展生存期（PFS）和总生存期（OS））之间关联的强度。
本荟萃分析研究最终纳入了包含8169例病例的41篇论文。其中，28篇文章是关于结直肠癌的，1篇是关于胃肠道癌（胃癌和结肠癌）的，11篇是关于胃癌的，1篇是关于结直肠癌和胃食管癌的。汇总所有符合条件的研究后，我们发现GSTP1 Ile105Val多态性与胃癌和结直肠癌化疗相关的肿瘤反应（G与A：OR 1.697，95%CI 1.191 - 2.418；GG与AA：OR 2.804，95%CI l.414 - 5.560；AG与AA：OR 1.540，95%CI 1.011 - 2.347；GG与AA+AG：OR 2.139，95%CI 1.256 - 3.641）、PFS（GG与AA，HR 0.640，95%CI 0.455 - 0.900；AG+GG与AA：HR 0.718，95%CI 0.562 - 0.919）和OS（AG与AA：HR 0.857，95%CI 0.746 - 0.986；GG与AA：HR 0.679，95%CI 0.523 - 0.882；AG+GG与AA：HR 0.663，95%CI 0.542 - 0.812）存在显著关联，且未发现该多态性与毒性之间存在显著关联。
GSTP1 Ile105Val多态性与胃癌和结直肠癌化疗后的肿瘤反应、PFS和OS相关。
