Giovannucci E, Stampfer M J, Colditz G A, Rimm E B, Trichopoulos D, Rosner B A, Speizer F E, Willett W C
Channing Laboratory, Department of Medicine, Harvard Medical School, Boston, Mass. 02115.
J Natl Cancer Inst. 1993 Jun 2;85(11):875-84. doi: 10.1093/jnci/85.11.875.
Reduced methylation of DNA may contribute to loss of the normal controls on proto-oncogene expression. In humans, hypomethylation of DNA has been observed in colorectal cancers and in their adenomatous polyp precursors. Accumulation of DNA methylation abnormalities, observed during progression of human colorectal neoplasia, may be influenced by certain dietary factors. The apparent protective effect of fresh fruits and vegetables, the major folate sources, on colorectal cancer incidence suggests that a methyl-deficient diet contributes to occurrence of this malignancy. Low dietary folate and methionine and high intake of alcohol may reduce levels of S-adenosylmethionine, which is required for DNA methylation.
To determine if dietary factors that may influence methyl availability are related to colorectal adenomas, we prospectively examined the association of folate, methionine, and alcohol intakes and risk of colorectal adenoma.
We assessed dietary intake for a 1-year period for women of the Nurses' Health Study, started in 1976, and for men of the Health Professionals Follow-up Study, started in 1986--using a semiquantitative food frequency questionnaire. Adenomatous polyps of the left colon or rectum were diagnosed in 564 of 15,984 women who had had an endoscopy between 1980 and 1990 and in 331 of 9490 men who had undergone an endoscopy between 1986 and 1990.
High dietary folate was inversely associated with risk of colorectal adenoma in women (multivariate relative risk [RR] = 0.66; 95% confidence interval [CI] = 0.46-0.95 between high and low quintiles of intake) and in men (RR = 0.63; 95% CI = 0.41-0.98) after adjusting for age, family history, indications for endoscopy, history of previous endoscopy, total energy intake, saturated fat intake, dietary fiber, and body mass index. Relative to nondrinkers, drinkers of more than 30 g of alcohol daily (about two drinks) had an elevated risk of adenoma (in women, RR = 1.84, 95% CI = 1.19-2.86; in men, RR = 1.64, 95% CI = 0.92-2.93). Methionine intake was inversely associated with risk of adenomas 1 cm or larger (RR = 0.62; 95% CI = 0.46-0.85, combining men and women).
Folate, alcohol, and methionine could influence methyl group availability, and a methyl-deficient diet may be linked to early stages of colorectal neoplasia. A dietary pattern that increases methyl availability could reduce incidence of colorectal cancer.
These data support efforts to increase dietary folate in segments of the population having diets with low intakes of this nutrient.
DNA甲基化水平降低可能导致原癌基因表达的正常调控缺失。在人类中，已在结直肠癌及其腺瘤性息肉前体中观察到DNA低甲基化。在人类结直肠肿瘤进展过程中观察到的DNA甲基化异常积累可能受某些饮食因素影响。新鲜水果和蔬菜是叶酸的主要来源，它们对结直肠癌发病率具有明显的保护作用，这表明甲基缺乏饮食会促使这种恶性肿瘤的发生。低膳食叶酸和蛋氨酸以及高酒精摄入量可能会降低DNA甲基化所需的S-腺苷甲硫氨酸水平。
为了确定可能影响甲基可利用性的饮食因素是否与结直肠腺瘤有关，我们前瞻性地研究了叶酸、蛋氨酸和酒精摄入量与结直肠腺瘤风险之间的关联。
我们使用半定量食物频率问卷，评估了始于1976年的护士健康研究中的女性以及始于1986年的卫生专业人员随访研究中的男性1年的饮食摄入量。在1980年至1990年间接受内镜检查的15984名女性中，有564人被诊断出左结肠或直肠有腺瘤性息肉；在1986年至1990年间接受内镜检查的9490名男性中，有331人被诊断出患有腺瘤性息肉。
在调整了年龄、家族史、内镜检查指征、既往内镜检查史、总能量摄入、饱和脂肪摄入、膳食纤维和体重指数后，高膳食叶酸摄入量与女性（多变量相对风险[RR]=0.66；摄入量最高和最低五分位数之间的95%置信区间[CI]=0.46 - 0.95）和男性（RR = 0.63；95% CI = 0.41 - 0.98）的结直肠腺瘤风险呈负相关。与不饮酒者相比，每天饮酒超过30克（约两杯）的饮酒者患腺瘤的风险升高（女性中，RR = 1.84，95% CI = 1.19 - 2.86；男性中，RR = 1.64，95% CI = 0.92 - 2.93）。蛋氨酸摄入量与直径1厘米或更大的腺瘤风险呈负相关（合并男性和女性，RR = 0.62；95% CI = 0.46 - 0.85）。
叶酸、酒精和蛋氨酸可能影响甲基基团的可利用性，甲基缺乏饮食可能与结直肠肿瘤的早期阶段有关。增加甲基可利用性的饮食模式可能会降低结直肠癌的发病率。
这些数据支持在叶酸摄入量低的人群中增加膳食叶酸的努力。
