Choi Jeong-hwa, Yates Zoe, Martin Charlotte, Boyd Lyndell, Ng Xiaowei, Skinner Virginia, Wai Ron, Veysey Martin, Lucock Mark
School of Environmental and Life Sciences, University of Newcastle.
J Nutr Sci Vitaminol (Tokyo). 2015;61(6):455-9. doi: 10.3177/jnsv.61.455.
Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. This study examined the association between PteGlu and 19bp del-DHFR, and adenomatous polyp (AP) occurrence, an antecedent of colorectal cancer. A total of 199 subjects (162 controls and 37 AP cases) were analysed to determine dietary intake of total folate, natural methylfolate and synthetic PteGlu, level of erythrocyte folate and plasma homocysteine (tHcy), and genotype of 19bp del-DHFR. Dietary folate intake, erythrocyte folate, tHcy and 19bp del-DHFR variants did not independently predict the occurrence of AP. However, a gene-nutrient interaction was observed when subjects were stratified according to dietary folate intake. In subjects with a folate intake above the median value due to significant dietary PteGlu content, the presence of the 19bp-deletion allele decreased the risk for AP (OR=0.35, 95% CI: 0.13-0.97). However, such association was not evident in individuals with a folate intake below the median value. In conclusion, the finding suggests that folate nutrition and 19bp del-DHFR variation may interact to modify AP risk.
叶酸及相关基因变异是结直肠癌病因中的重要风险因素。二氢叶酸还原酶（DHFR）在合成叶酸（蝶酰单谷氨酸，PteGlu）吸收后代谢为四氢叶酸的过程中起关键作用。因此，DHFR的19bp缺失变异可能导致叶酸相关的结直肠疾病易感性改变。本研究调查了PteGlu与19bp del-DHFR以及腺瘤性息肉（AP）发生（结直肠癌的前驱病变）之间的关联。共分析了199名受试者（162名对照和37例AP病例），以确定总叶酸、天然甲基叶酸和合成PteGlu的膳食摄入量、红细胞叶酸水平和血浆同型半胱氨酸（tHcy）以及19bp del-DHFR的基因型。膳食叶酸摄入量、红细胞叶酸、tHcy和19bp del-DHFR变异并不能独立预测AP的发生。然而，当根据膳食叶酸摄入量对受试者进行分层时，观察到了基因-营养素相互作用。在因膳食中PteGlu含量显著而叶酸摄入量高于中位数的受试者中，19bp缺失等位基因的存在降低了AP风险（OR=0.35，95%CI：0.13-0.97）。然而，在叶酸摄入量低于中位数的个体中，这种关联并不明显。总之，该研究结果表明叶酸营养和19bp del-DHFR变异可能相互作用以改变AP风险。
