Sibertin-Blanc Camille, Mancini Julien, Fabre Aurélie, Lagarde Arnaud, Del Grande Jean, Levy Nicolas, Seitz Jean-François, Olschwang Sylviane, Dahan Laetitia
Department of Digestive Oncology, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France; UMR S-910 INSERM, Medical Genetics and Functional Genomics, Aix-Marseille University, Marseille, France.
Department of Biostatistics, Assistance Publique Hôpitaux de Marseille, Marseille, France; UMR_S912, Economic & Social Sciences, Health Systems & Medical Informatics, SESSTIM, Aix Marseille Université, Inserm, IRD, Marseille, France.
Dig Liver Dis. 2015 Apr;47(4):331-7. doi: 10.1016/j.dld.2014.12.013. Epub 2014 Dec 30.
No predictive marker has been yet identified for bevacizumab which is widely used in metastatic colorectal cancer.
Evaluate impact of single nucleotide polymorphisms involved in Vascular Endothelial Growth Factor pathway on efficacy and tolerance of bevacizumab.
We retrospectively included patients who were treated with bevacizumab-based chemotherapy for metastatic colorectal cancer, and for whom a deoxyribonucleic acid sample was available. Ten polymorphisms in Vascular Endothelial Growth Factor-A, his receptors and hypoxia inducible factor-1α were genotyped on germ line DNA using real-time polymerase chain reaction TaqMan(®).
89 patients were included. The CC genotype for rs3025039 (Vascular Endothelial Growth Factor-A c.*237C>T) was associated with a significantly better time to treatment failure (14.2 months) as compared to the CT and TT genotypes (6.0 months) in univariate (p = 0.004) and multivariate (p = 0.022; HR = 0.57; 95% CI [0.35-0.92]) analysis. Patients with at least one T allele showed worse overall survival and progression-free survival as compared to homozygous CC patients in univariate analysis (respectively p = 0.016 and p = 0.044). There was significantly more severe hypertension for the CC genotype (29.5%) compared to CT and TT genotypes (7.1%) (p = 0.022) in multivariate analysis.
In this retrospective study, the rs3025039 polymorphism was significantly associated with time to treatment failure and hypertension in patients treated with bevacizumab-based chemotherapy.
在广泛应用于转移性结直肠癌的贝伐单抗治疗中，尚未发现预测性标志物。
评估血管内皮生长因子途径中涉及的单核苷酸多态性对贝伐单抗疗效和耐受性的影响。
我们回顾性纳入了接受基于贝伐单抗的化疗治疗转移性结直肠癌且有脱氧核糖核酸样本的患者。使用实时聚合酶链反应TaqMan（®）对血管内皮生长因子-A、其受体和缺氧诱导因子-1α中的10个多态性进行种系DNA基因分型。
纳入89例患者。在单因素（p = 0.004）和多因素（p = 0.022；HR = 0.57；95% CI [0.35 - 0.92]）分析中，rs3025039（血管内皮生长因子-A c.*237C>T）的CC基因型与治疗失败时间显著更长（14.2个月）相关，而CT和TT基因型为（6.0个月）。在单因素分析中，与纯合CC患者相比，至少有一个T等位基因的患者总生存期和无进展生存期更差（分别为p = 0.016和p = 0.044）。在多因素分析中，CC基因型的严重高血压发生率（29.5%）显著高于CT和TT基因型（7.1%）（p = 0.022）。
在这项回顾性研究中，rs3025039多态性与接受基于贝伐单抗的化疗患者的治疗失败时间和高血压显著相关。
