葉酸、亞甲基四氫葉酸還原酶基因多型性及同半胱胺酸與大腸直腸癌危險性之關係

葉酸在大腸直腸癌進展過程中扮演重要的角色，單碳代謝中 5,10-亞甲基四氫葉酸還原酶（5,10-methylenetetrahydrofolate reductase, MTHFR)是葉酸代謝的重要酵素，參與5,10-亞甲基四氫葉酸（5,10-methylenetetrahydrofolate）轉換為5-甲基四氫葉酸（5-methyltetrahydrofolate），此過程會提供一個甲基將同半胱胺酸（homocysteine）轉為甲硫胺酸（methionine）。研究發現 MTHFR 677C→T 基因多型性中，帶有突變對偶基因 TT 型對於罹患大腸直腸癌有保護作用，但結果並不一致。因此，本研究目的為探討葉酸、亞甲基四氫葉酸還原酶基因多型性（MTHFR 677C→T）及同半胱胺酸與罹患大腸直腸癌危險性之關係。本研究是以醫院為基礎的病例對照研究，於台中榮民總醫院共募集 168 位大腸直腸癌受試者（病例組）及 188 位健康受試者（對照組），抽取其空腹血液分析血清葉酸濃度、 MTHFR 677C→T 基因型及血漿同半胱胺酸濃度。結果顯示，基因型為 CC 型的病例組其血清葉酸及血漿同半胱胺酸濃度顯著高於基因型為 CC 型的對照組。病例組帶有突變 T 對偶基因（CT型 + TT型）之血漿同半胱胺酸濃度顯著高於對照組帶有突變 T 對偶基因者。無論是否調整相關干擾因子後，MTHFR 677C→T 基因型與血清葉酸及血漿同半胱胺酸濃度皆無顯著的相關性，但血清葉酸與血漿同半胱胺酸呈顯著負相關（β=-0.07,p＜0.001）。血清葉酸濃度（OR,1.07;95% CI,1.03-1.10）及血漿同半胱胺酸濃度（OR,1.32; 95% CI,1.20-1.45）會增加罹患大腸直腸癌的危險性，但 MTHFR 677C→T 基因型對罹患大腸直腸癌的勝算比則無顯著影響。高血漿同半胱胺酸濃度是增加罹患大腸直腸癌的重要危險因子，但血清葉酸與大腸直腸癌的關係則需要進一步研究。

關鍵字

葉酸；亞甲基四氫葉酸還原酶基因多型性；同半胱胺酸；大腸直腸癌

並列摘要

Folate plays an important role in the progression of colorectal cancer (CRC). 5,10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in one carbon metabolism, which converts the 5,10-methylenetetrahydrofolate to the 5-methyltetrahydrofolate and the reaction provides a methyl group for homocysteine to convert methionine. Previous studies reported that MTHFR 677C→T gene polymorphism which there was mutation in T allele had a decreased risk of CRC. However, the results of the association of MTHFR 677C→T gene polymorphism with colorectal cancer were quite inconsistent. Therefore, the purpose of this study was to investigate the association of serum folate, MTHFR 677C→T gene polymorphism and plasma homocysteine with the risk of CRC. This study was a case-control study. Patients with CRC and healthy subjects were recruited from Taichung Veterans General Hospital and were assigned to either the case group (n = 168) or the control group (n = 188). Fasting blood samples were drawn to measure serum folate, MTHFR 677C→T genotypes and plasma homocysteine. Results showed serum folate and homocysteine concentrations of the case group with CC genotype were higher than the control group with CC genotype. Plasma homocysteine in the case group with T-allele mutation (CT genotype + TT genotype) were higher than the control group with T-allele mutation. Whether or not adjusting the confounding factors, there was no significant association of MTHFR 677C→T genotypes with serum folate and plasma homocysteine concentration. However, serum folate was strongly inversely associated with plasma homocysteine (β= -0.07, p＜0.001). Serum folate (OR, 1.07; 95 % CI, 1.03-1.10) and plasma homocysteine concentration (OR, 1.32; 95 % CI, 1.20-1.45) significantly increased the risk of CRC. Nevertheless, MTHFR 677C→T genotypes had no effect on the risk of CRC. High plasma homocysteine concentration might be a risk factor for CRC, while the association between serum folate and CRC need further study.

並列關鍵字

folate ； methylenetetrahydrofolate reductase gene polymorphism ； homocysteine ； colorectal cancer

參考文獻

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葉酸、亞甲基四氫葉酸還原酶基因多型性及同半胱胺酸與大腸直腸癌危險性之關係

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