Dong Ningning, Meng Fandong, Wu Yongdong, Wang Mingyu, Cui Yongchun, Zhang Shutian
Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, 95 Yong-an Road, Xi-cheng District, Beijing, 100050, China.
Chemotherapy Department, Shandong Tumor Hospital and Institute, Jinan, China.
Tumour Biol. 2015 Sep;36(10):7691-8. doi: 10.1007/s13277-015-3492-1. Epub 2015 May 2.
The purpose of this study is to evaluate the influence of germline polymorphisms of cytochrome P450 (CYP450) on objective response, progression-free survival (PFS) and overall suruvival (OS) in metastatic colorectal cancer (mCRC) receiving the combination chemotherapy of irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI). All SNPs in CYP450, whose minor allele frequency were more than 10 %, were genotyped in 82 patients with mCRC who received first-line FOLFIRI regimen. χ (2) test or Fisher's exact test was used to assess the correlation between SNPs and objective response as appropriate and log-rank test between SNPs and PFS or OS. Cox proportional hazards models were used to analyze the association of CYP450 gene polymorphisms and clinical factors for PFS and OS. No SNP showed predictive or prognostic value for clinical outcomes, except for CYP3A5 rs776746 A>G, which was significantly associated with PFS (P = 0.0002). Multivariate analysis confirmed its prognostic value for PFS (P = 0.002). CYP3A5 rs776746 A>G polymorphisms have a prognostic contribution toward FOLFIRI regimen in mCRC. This could represent a further step toward personalized therapy.
本研究旨在评估细胞色素P450（CYP450）种系多态性对接受伊立替康、5-氟尿嘧啶和亚叶酸钙联合化疗（FOLFIRI）的转移性结直肠癌（mCRC）患者客观缓解率、无进展生存期（PFS）和总生存期（OS）的影响。对82例接受一线FOLFIRI方案治疗的mCRC患者进行了CYP450中次要等位基因频率大于10%的所有单核苷酸多态性（SNP）基因分型。采用χ²检验或Fisher精确检验评估SNP与客观缓解率之间的相关性，并采用对数秩检验评估SNP与PFS或OS之间的相关性。采用Cox比例风险模型分析CYP450基因多态性与PFS和OS临床因素之间的关联。除CYP3A5 rs776746 A>G与PFS显著相关（P = 0.0002）外，没有SNP显示出对临床结局的预测或预后价值。多因素分析证实了其对PFS的预后价值（P = 0.002）。CYP3A5 rs776746 A>G多态性对mCRC患者的FOLFIRI方案有预后影响。这可能是迈向个性化治疗的又一步。
