Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia.
J Nutr. 2011 Feb;141(2):274-83. doi: 10.3945/jn.110.131235. Epub 2010 Dec 22.
Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett's esophagus (BE), a precancerous lesion, remain unexplored. We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC.
叶酸在 DNA 合成和甲基化中起着关键作用。有限的证据表明，高摄入量可能会降低整体食管癌的风险；然而，与食管癌亚型和巴雷特食管（BE，一种癌前病变）的关联仍未得到探索。我们评估了叶酸、B 族维生素和来自食物和补充剂的甲基供体（蛋氨酸、胆碱、甜菜碱）的摄入量、关键叶酸代谢基因的多态性与 BE、食管腺癌（EAC）和食管鳞状细胞癌（ESCC）的风险之间的关系，这两项研究是在澳大利亚进行的两项基于人群的病例对照研究中进行的。无（n = 266）或有（n = 101）异型增生的 BE 患者与人群对照（n = 577）进行比较；同样，EAC（n = 636）或 ESCC（n = 245）患者与人群对照（n = 1507）进行比较，使用多变量调整的逻辑回归。从食物中摄入叶酸增加与 EAC 风险降低相关（P 趋势=0.01），并减轻了与吸烟和饮酒相关的 ESCC 风险增加。相比之下，补充叶酸与 BE 伴异型增生的风险显著升高相关。从食物中摄入高量核黄素和蛋氨酸与 EAC 风险增加相关，而增加甜菜碱摄入量与 BE 无异型增生（P 趋势=0.004）或有异型增生（P 趋势=0.02）的风险降低相关。补充硫胺素、核黄素、烟酸和维生素 B-12 与 EAC 风险增加相关。在所研究的遗传多态性与 BE 或 EAC 风险之间没有一致的关联。富含叶酸的食物摄入可能降低 EAC 的风险，但我们的数据提示叶酸补充剂可能会增加 BE 伴异型增生和 EAC 的风险。
