Slattery Martha L, Curtin Karen, Sweeney Carol, Levin Theodore R, Potter John, Wolff Roger K, Albertsen Hans, Samowitz Wade S
Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT 84108, USA.
Int J Cancer. 2007 Feb 1;120(3):656-63. doi: 10.1002/ijc.22342.
It has been proposed that dietary factors such as folate, alcohol and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large population-based case-control study of incident colon cancer were used to evaluate whether intake of dietary, obesity, physical activity and nonsteroidal antiinflammatory drugs are associated with a CpG island methylator phenotype (CIMP). The BRAF V600E mutation and 5 CpG island markers (MINT1, MINT2, MINT31, p16 and hMLH1) were assessed in 1154 cases of colon cancer. We hypothesized that dietary factors involved in DNA methylation, cruciferous vegetables and use of aspirin/NSAIDs would be associated with CIMP-high tumors. Dietary folate, vitamins B(6) and B(12), methionine and alcohol were not associated with increased likelihood of colon tumors with the CIMP-high (2 or more markers methylated) phenotype. Dietary fiber, physical activity and aspirin and other nonsteroidal antiinflammatory drugs were inversely associated with both CIMP-low and CIMP-high tumors. Our results also suggested non-CIMP pathways as well. Obese individuals were at 2-fold increased risk of having a CIMP-low tumor. Alcohol was associated with an increased risk of tumors that were MSI+ and CIMP-low. In the presence of smoking 20 or more cigarettes per day, use of NSAIDs did not protect against a BRAF mutation. Our data suggest multiple pathways to colon cancer. They do not support a unique role for dietary folate, alcohol, vitamins B(6) and B(12) and methionine in a CpG island methylator phenotype.
有人提出，叶酸、酒精和蛋氨酸等饮食因素可能与结肠癌有关，因为它们参与了DNA甲基化过程。一项基于大量人群的结肠癌病例对照研究数据被用于评估饮食摄入、肥胖、身体活动和非甾体抗炎药是否与CpG岛甲基化表型（CIMP）相关。在1154例结肠癌病例中评估了BRAF V600E突变和5个CpG岛标记物（MINT1、MINT2、MINT31、p16和hMLH1）。我们假设参与DNA甲基化的饮食因素、十字花科蔬菜以及阿司匹林/非甾体抗炎药的使用与CIMP高的肿瘤相关。饮食中的叶酸、维生素B6和B12、蛋氨酸和酒精与CIMP高（2个或更多标记物甲基化）表型的结肠肿瘤发生可能性增加无关。膳食纤维、身体活动以及阿司匹林和其他非甾体抗炎药与CIMP低和CIMP高的肿瘤均呈负相关。我们的结果还提示了非CIMP途径。肥胖个体患CIMP低肿瘤的风险增加两倍。酒精与微卫星高度不稳定（MSI+）且CIMP低的肿瘤风险增加有关。在每天吸烟20支或更多的情况下，使用非甾体抗炎药不能预防BRAF突变。我们的数据提示结肠癌存在多种发病途径。它们不支持饮食中的叶酸、酒精、维生素B6、B12和蛋氨酸在CpG岛甲基化表型中具有独特作用。
