叶酸摄入、饮酒与亚甲基四氢叶酸还原酶（MTHFR）C677T 基因多态性：对前列腺癌风险的影响及其相互作用。
Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: influence on prostate cancer risk and interactions.
机构信息
Department of Community Health and Epidemiology, Queen's University Kingston, ON, Canada.
出版信息
Front Oncol. 2012 Aug 14;2:100. doi: 10.3389/fonc.2012.00100. eCollection 2012.
PURPOSE
Folate is essential to DNA methylation and synthesis and may have a complex dualistic role in prostate cancer. Alcohol use may increase risk and epigenetic factors may interact with lifestyle exposures. We aimed to characterize the independent and joint effects of folate intake, alcohol consumption, and the MTHFR C677T gene polymorphism on prostate cancer risk, while accounting for intakes of vitamins B(2), B(6), B(12), methionine, total energy, and confounders.
METHODS
A case-control study was conducted at Kingston General Hospital of 80 incident primary prostate cancer cases and 334 urology clinic controls, all with normal age-specific PSA levels (to exclude latent prostate cancers). Participants completed a questionnaire on folate and alcohol intakes and potential confounders prior to knowledge of diagnosis, eliminating recall bias, and blood was drawn for MTHFR genotyping. Joint effects of exposures were assessed using unconditional logistic regression and significance of multiplicative and additive interactions using general linear models.
RESULTS
Folate, vitamins B(2), B(6), B(12), methionine, and the CT and TT genotypes were not associated with prostate cancer risk. The highest tertile of lifetime alcohol consumption was associated with increased risk (OR = 2.08; 95% CI: 1.12-3.86). Consumption of >5 alcoholic drinks per week was associated with increased prostate cancer risk among men with low folate intake (OR = 2.38; 95% CI: 1.01-5.57), and higher risk among those with the CC MTHFR genotype (OR = 4.43; 95% CI: 1.15-17.05). Increased risk was also apparent for average weekly alcohol consumption when accounting for the multiplicative interaction between folate intake and MTHFR C677T genotype (OR = 3.22; 95% CI: 1.36-7.59).
CONCLUSION
Alcohol consumption is associated with increased prostate cancer risk, and this association is stronger among men with low folate intake, with the CC MTHFR genotype, and when accounting for the joint effect of folate intake and MTHFR C677T genotype.
目的
叶酸对 DNA 甲基化和合成至关重要，在前列腺癌中可能具有复杂的双重作用。饮酒可能会增加风险，而表观遗传因素可能与生活方式暴露相互作用。我们旨在描述叶酸摄入、饮酒量和 MTHFR C677T 基因多态性对前列腺癌风险的独立和联合作用，同时考虑到维生素 B(2)、B(6)、B(12)、蛋氨酸、总能量和混杂因素的摄入量。
方法
在金斯敦综合医院对 80 例新发原发性前列腺癌病例和 334 例泌尿科诊所对照进行了病例对照研究，所有病例的年龄特异性 PSA 水平均正常（排除潜伏性前列腺癌）。参与者在知晓诊断之前完成了关于叶酸和饮酒摄入量以及潜在混杂因素的问卷，从而消除了回忆偏倚，并抽取了血液进行 MTHFR 基因分型。使用非条件逻辑回归评估暴露的联合效应，并使用广义线性模型评估乘法和加法交互作用的显著性。
结果
叶酸、维生素 B(2)、B(6)、B(12)、蛋氨酸以及 CT 和 TT 基因型与前列腺癌风险无关。终生饮酒量最高的三分位与风险增加相关（OR=2.08；95%CI：1.12-3.86）。每周饮酒量超过 5 杯与低叶酸摄入量男性的前列腺癌风险增加相关（OR=2.38；95%CI：1.01-5.57），而与 CC MTHFR 基因型男性的相关性更高（OR=4.43；95%CI：1.15-17.05）。当考虑叶酸摄入量与 MTHFR C677T 基因型之间的乘法交互作用时，每周平均饮酒量与前列腺癌风险增加也明显相关（OR=3.22；95%CI：1.36-7.59）。
结论
饮酒与前列腺癌风险增加相关，而这种相关性在叶酸摄入量低、CC MTHFR 基因型和考虑叶酸摄入量与 MTHFR C677T 基因型联合效应时更强。
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