Yeh Chih-Ching, Lai Ching-Yu, Chang Shih-Ni, Hsieh Ling-Ling, Tang Reiping, Sung Fung-Chang, Lin Yi-Kuei
School of Public Health, College of Public Health, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 110, Taiwan.
Department of Public Health, College of Public Health, China Medical University, 91 Hsieh-Shih Road, Taichung, 404, Taiwan.
Int J Clin Oncol. 2017 Jun;22(3):484-493. doi: 10.1007/s10147-016-1080-z. Epub 2017 Jan 2.
This study examined the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and survival of patients with colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)-based chemotherapy in Taiwan.
We genotyped MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) for 498 CRC patients treated with 5-FU-based chemotherapy after receiving surgery. Survival analyses on MTHFR polymorphisms were performed using log-rank test and Kaplan-Meier curve. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MTHFR genotypes and survival.
Overall survival (OS) was significantly longer in CRC patients with MTHFR 677 CT+TT genotypes compared with those with 677 CC genotype (HR 0.77; 95% CI 0.60-0.98). Although the MTHFR A1298C polymorphism was not associated with OS in CRC, this polymorphism was associated with significantly shorter OS in rectal cancer. Among rectal cancer patients, OS was shorter for patients with AC+CC genotypes than for those with the AA genotype (HR 1.95; 95% CI 1.35-2.83). In haplotype analysis, better OS was found for colon cancer patients carrying the MTHFR 677T-1298A haplotype (HR 0.73; 95% CI 0.55-0.97), but worse survival was linked to rectal cancer patients carrying the MTHFR 677C-1298C haplotype (HR 1.53; 95% CI 1.08-2.18).
Our findings suggest that MTHFR genotypes provide prognostic information for CRC patients treated with 5-FU-based chemotherapy.
本研究探讨了台湾地区接受以5-氟尿嘧啶（5-FU）为基础化疗的结直肠癌（CRC）患者中，亚甲基四氢叶酸还原酶（MTHFR）基因多态性与生存情况之间的关联。
我们对498例接受手术治疗后再接受以5-FU为基础化疗的CRC患者的MTHFR基因多态性C677T（rs1801133）和A1298C（rs1801131）进行基因分型。采用对数秩检验和Kaplan-Meier曲线对MTHFR基因多态性进行生存分析。使用Cox比例风险模型计算MTHFR基因分型与生存之间关联的风险比（HR）和95%置信区间（CI）。
与677 CC基因型的CRC患者相比，677 CT+TT基因型的患者总生存期（OS）显著更长（HR 0.77；95% CI 0.60 - 0.98）。虽然MTHFR A1298C基因多态性与CRC患者的OS无关，但该多态性与直肠癌患者的OS显著缩短有关。在直肠癌患者中，AC+CC基因型患者的OS短于AA基因型患者（HR 1.95；95% CI 1.35 - 2.83）。在单倍型分析中，携带MTHFR 677T-1298A单倍型的结肠癌患者OS较好（HR 0.73；95% CI 0.55 - 0.97），但携带MTHFR 677C-1298C单倍型的直肠癌患者生存较差（HR 1.53；95% CI 1.08 - 2.18）。
我们的研究结果表明，MTHFR基因分型可为接受以5-FU为基础化疗的CRC患者提供预后信息。
