A Study of the MTHFR Gene Polymorphism C677T in Colorectal Cancer
A Study of the MTHFR Gene Polymorphism C677T in Colorectal Cancer
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DOI：
10.3816/ccc.2009.n.007
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发表时间：
2009-01-01
影响因子：
3.4
通讯作者：
Gustavsson, Bengt
中科院分区：
文献类型：
--
作者：
Derwinger, Kristoffer;Wettergren, Yvonne;Gustavsson, Bengt
目的：探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性在结直肠癌中的临床意义。该研究假设该基因可能会影响癌症发展的风险和癌症治疗的结果。患者和方法：随机抽取1999年至2006年在我科接受治疗的所有结直肠癌患者中的30%(n=544)进行基因分型(n=1812)。对基本的临床和病理因素按基因型组进行分析，并与整个队列进行比较。按基因分型分析化疗的耐受性和可能的不良反应。对1999至2003年间接受治疗的患者的所有阶段的存活率按基因进行分析。并与健康献血员的对照资料进行了比较。结果：没有基因分型与结直肠癌风险增加或更高的癌症分期相关。携带CT/TT基因的患者发生氟尿嘧啶(5-FU)治疗不良反应的风险显著增加(P<；0.05)。在III期结肠癌中，CT/TT基因携带者预后较CC基因携带者差。单因素(P<；.003)和多因素(P<；.040)分析显示差异有统计学意义。虽然与基因型相关的副作用风险仍处于IV期，但对生存率的影响并不显著(P<；.1)。结论：在我们的材料中，MTHFR基因C677T多态性不影响结直肠癌的风险，但它可以影响对化疗的敏感性和副作用的风险，从而影响III期和可能IV期结肠癌的生存。它可能是未来选择治疗方案的预测因素。
Purpose: The aim of this study was to examine the clinical significance of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T in colorectal cancer (CRC). The hypothesis was that the genotype could affect the risk of cancer development and the results of cancer treatment. Patients and Methods: Genotyping was made for a random 30% (n = 544) of all patients treated for CRC at our unit from 1999 to 2006 (n = 1812). Basic clinical and pathologic factors were analyzed by genotype group and also compared with those of the entire cohort. Tolerability of chemotherapy and possible side effects were analyzed by genotype. Survival was analyzed by genotype for all stages for patients treated between 1999 and 2003. The genotype prevalence was also compared with a control material of healthy blood donors. Results: No genotype was associated with an increased risk of CRC or higher cancer stage. The patients with CT/TT genotype had significantly greater risk of suffering side effects from fluoropyrimidine (5-fluorouracil) treatment (P < .05). In stage III colon cancer the patients with CT/TT genotype had a poorer prognosis than those with the CC genotype. The difference was significant in univariate (P < .003) and multivariate (P < .040) analysis. Though the genotype-associated side effect risks remained in stage IV, the effect on survival was not significant (P < .1). Conclusion: The MTHFR polymorphism C677T does, in our material, not affect the risk of CRC; however, it can affect the sensitivity to chemotherapy and the risk of side-effects and therefore survival in stage III and possibly stage IV colon cancer It could be a future predictive factor in the choice of a treatment regimen.