Van Guelpen Bethany R, Wirén Sara M, Bergh Anders R J, Hallmans Göran, Stattin Pär E, Hultdin Johan
Department of Medical Biosciences, Clinical Chemistry, Umeå University Hospital, Sweden.
Eur J Cancer Prev. 2006 Feb;15(1):46-50. doi: 10.1097/01.cej.0000186640.19872.4d.
It has been proposed that folate and polymorphisms of the enzyme methylenetetrahydrofolate reductase (MTHFR), which regulates influx of folate from DNA synthesis and repair to methylation reactions, are involved in the aetiology of cancer. To relate the MTHFR 677C-->T and 1298A-->C polymorphisms to the risk of prostate cancer, taking into consideration prospective plasma levels of folate, vitamin B12 and homocysteine. The design was a case-control study of 223 prostate cancer cases and 435 matched controls nested within the population-based Northern Sweden Health and Disease Cohort. Neither the MTHFR 677C-->T nor the MTHFR 1298A-->C polymorphism was statistically significantly associated with the risk of prostate cancer in univariate analysis by conditional logistic regression. After adjustment for MTHFR 1298A-->C, plasma folate, vitamin B12, homocysteine, body mass index and smoking, the odds ratios were, for the 677 CT genotype, 1.52 [95% confidence interval (CI) 1.02-2.26], and for TT, 0.91 (95% CI 0.41-2.04). Our previously reported observation of a possible increase in the risk of prostate cancer at high plasma folate levels was attributable in this study to subjects having the MTHFR 677C-->T polymorphism. We found that the MTHFR 677C-->T polymorphism is not likely to have a major role in the development of prostate cancer, although it may possibly increase the risk in combination with high plasma folate levels. Further investigation in larger studies is warranted.
有人提出，叶酸以及亚甲基四氢叶酸还原酶（MTHFR）的多态性参与了癌症的病因学，该酶调节着叶酸从DNA合成与修复到甲基化反应的流入。为了将MTHFR 677C→T和1298A→C多态性与前列腺癌风险相关联，同时考虑叶酸、维生素B12和同型半胱氨酸的前瞻性血浆水平。本研究设计为一项病例对照研究，在基于人群的瑞典北部健康与疾病队列中纳入了223例前列腺癌病例和435例匹配对照。在单因素条件逻辑回归分析中，MTHFR 677C→T和MTHFR 1298A→C多态性均与前列腺癌风险无统计学显著关联。在对MTHFR 1298A→C、血浆叶酸、维生素B12、同型半胱氨酸、体重指数和吸烟进行调整后，677 CT基因型的比值比为1.52 [95%置信区间（CI）1.02 - 2.26]，TT基因型为0.91（95% CI 0.41 - 2.04）。在本研究中，我们之前报道的高血浆叶酸水平时前列腺癌风险可能增加的观察结果归因于具有MTHFR 677C→T多态性的受试者。我们发现，MTHFR 677C→T多态性在前列腺癌发生中不太可能起主要作用，尽管它可能与高血浆叶酸水平共同增加风险。有必要在更大规模的研究中进一步调查。
