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首页> 外文期刊>Pharmacogenetics and genomics >Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI+bevacizumab.
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Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI+bevacizumab.

机译：SHMT1基因多态性对一线FOLFIRI +贝伐单抗治疗的转移性结直肠癌患者临床结局的影响。

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摘要

The impact of thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and serine hydroxymethyltransferase 1 (SHMT1) gene polymorphisms and that of dihydropyrimidine dehydrogenase (DPD) enzyme activity, serum total homocysteine level, and estimated serum creatinine clearance on first-line 5-fluorouracil, leucovorin, irinotecan, and bevacizumab (FOLFIRI+bevacizumab) regimen efficacy in metastatic colorectal cancer patients was investigated. DNA was extracted from peripheral blood mononuclear cells. Genotyping was performed for TYMS 5'UTR variable number tandem repeat, TYMS 3'UTR ins/del, MTHFR C677T, and SHMT1 C1420T polymorphisms. The DPD activity of peripheral blood mononuclear cells was also determined. The univariate and multivariate analyses demonstrated that the SHMT1 1420T allele was associated with better response (P=0.025) and longer progression-free survival (PFS) (P=0.00004) and overall survival (OS) (P=0.034). Grade >/=2 hypertension was also an independent prognostic factor of longer progression-free survival and OS. Bevacizumab-related hypertension might be a predictive marker of treatment efficacy (P=0.0002 for OS) in the case of wild (CC) SHMT1 1420 genotypes only.
机译：胸腺嘧啶合酶（TYMS），亚甲基四氢叶酸还原酶（MTHFR）和丝氨酸羟甲基转移酶1（SHMT1）基因多态性以及二氢嘧啶脱氢酶（DPD）酶活性，血清总同型半胱氨酸水平和估计的血清肌酐清除率对一线5的影响研究了氟尿嘧啶，亚叶酸钙，伊立替康和贝伐单抗（FOLFIRI +贝伐单抗）在转移性结直肠癌患者中的治疗效果。从外周血单核细胞中提取DNA。对TYMS 5'UTR可变数目串联重复，TYMS 3'UTR ins / del，MTHFR C677T和SHMT1 C1420T多态性进行基因分型。还测定了外周血单核细胞的DPD活性。单因素和多因素分析表明，SHMT1 1420T等位基因与较好的应答（P = 0.025）和更长的无进展生存期（PFS）（P = 0.00004）以及总生存期（OS）（P = 0.034）相关。 > / = 2级高血压也是更长的无进展生存期和OS的独立预后因素。仅在野生型（CC）SHMT1 1420基因型的情况下，与贝伐单抗相关的高血压可能是治疗功效的预测指标（对于OS，P = 0.0002）。

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