Morita Makiko, Yin Guang, Yoshimitsu Shin-ichiro, Ohnaka Keizo, Toyomura Kengo, Kono Suminori, Ueki Takashi, Tanaka Masao, Kakeji Yoshihiro, Maehara Yoshihiko, Okamura Takeshi, Ikejiri Koji, Futami Kitaroh, Maekawa Takafumi, Yasunami Yohichi, Takenaka Kenji, Ichimiya Hitoshi, Terasaka Reiji
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan E-mail :
Asian Pac J Cancer Prev. 2013;14(11):6249-56. doi: 10.7314/apjcp.2013.14.11.6249.
One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 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 B2, vitamin B6, and vitamin B12 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 B12 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 B6. 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.
一碳代谢在结直肠癌发生过程中发挥着重要作用。荟萃分析表明，叶酸和维生素B6的摄入与结直肠癌之间存在保护性关联，这主要基于对白种人的研究，且与叶酸代谢相关的基因多态性一直是人们关注的焦点。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。在一项针对日本816例病例和815名社区对照的研究中，我们调查了叶酸、蛋氨酸、维生素B2、维生素B6和维生素B12的饮食摄入量与结直肠癌风险之间的关联。在685例病例和778名对照中检测了与MTR 2756A>G、MTRR 66A>G和TSER重复多态性的关联。蛋氨酸和维生素B12的摄入量与结直肠癌风险呈负相关，但这些关联完全被饮食中的钙和n-3脂肪酸所混淆。即使不调整钙和n-3脂肪酸，其他营养素与风险也无关联。TSER 2R等位基因与风险增加呈剂量依赖性相关。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-营养素相互作用，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。本研究不支持叶酸和维生素B6具有保护性关联的观点。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。
