Folate-Related Nutrients, Genetic Polymorphisms, and Colorectal Cancer Risk: the Fukuoka Colorectal Cancer Study
Folate-Related Nutrients, Genetic Polymorphisms, and Colorectal Cancer Risk: the Fukuoka Colorectal Cancer Study
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DOI：
10.7314/apjcp.2013.14.11.6249
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Terasaka, Reiji
中科院分区：
文献类型：
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作者：
Morita, Makiko;Yin, Guang;Terasaka, Reiji
单碳代谢在结直肠癌发生中起重要作用。基于对高加索人的研究，荟萃分析表明叶酸和维生素B-6摄入与结直肠癌之间存在保护性联系，而与叶酸代谢有关的遗传多态性一直是人们感兴趣的问题。蛋氨酸合成酶（MTR）和胸苷酸合成酶（TS）多态性在结直肠癌发生中的作用研究较少。在一项对日本816例病例和815例社区对照的研究中，我们调查了叶酸、蛋氨酸、维生素B-2、维生素B-6和维生素B-12的膳食摄入量与结直肠癌风险的关系。在685例和778例对照中检测了与MTR 2756A>G、MTRR 66A>G和TSER重复多态性的关系。蛋氨酸和维生素B-12的摄入量与结直肠癌风险呈负相关，但这种关联完全被饮食中的钙和n-3脂肪酸所混淆。即使没有钙和n-3脂肪酸的调整，其他营养素也没有显示出与风险的关联。TSER 2R等位基因与风险增加呈剂量依赖性。MTR和MTRR多态性与结直肠癌风险无关。没有可测量的基因-基因或基因-营养相互作用，但与TSER 2R等位基因相关的风险增加似乎仅限于叶酸水平高的个体。这项研究不支持叶酸和维生素B-6的保护性联系。TSER 2R等位基因可能会增加患结直肠癌的风险。TSER多态性在结直肠癌发生中的作用可能因种族而异。
One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B-6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B-2, vitamin B-6, and vitamin B-12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B-12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B-6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.