Molecular Epidemiology on insulin-like growth facto (IGF) and colorectal adenomas

本文结合胰岛素样生长因子(IGF)及相关条件，对结直肠腺瘤的病因进行了研究。对3370人的冰冻血浆标本进行了IGF-I、IGFBP-3和C-肽的检测，并研究了叶酸、酒精和胆汁酸代谢的遗传多态与结直肠腺瘤风险的关系。代谢综合征伴随持续的高胰岛素血症，与结直肠腺瘤的风险增加密切相关。糖耐量异常和高C肽水平(衡量高胰岛素血症)也与腺瘤风险增加相关，但IGF-I和IGFBP-3都与结直肠腺瘤无关。与高血糖或高胰岛素血症相关的结直肠腺瘤的风险增加可能与IGF系统以外的一个或多个机制有关。叶酸相关的基因多态，据报道与结直肠癌相关，但与结直肠腺瘤无关。ALDH2基因多态也不存在。然而，一种合成胆汁酸的酶--CYP7A1的多态性与右侧结肠腺瘤有关，这表明胆汁酸与右侧结肠的癌变有关。吸烟和饮酒都与结直肠腺瘤的风险增加有关，尤其是远端腺瘤。研究发现，咖啡对糖尿病有保护作用，糖尿病是结直肠腺瘤的重要危险因素。吸烟和饮酒与糖耐量下降有关。研究发现，高乳制品和水果摄入量的饮食模式不仅与降低结直肠腺瘤的风险有关，而且对糖耐量异常也有保护作用

Etiological factors of colorectal adenomas were studied with special reference to insulin like growth factor (IGF) and related conditions. Frozen plasma samples of 3370 persons were used to measure IGF-I, IGFBP-3 and C-peptide, and genetic polymorphisms regarding folate, alcohol and bile acid metabolism were investigated in relation to colorectal adenoma risk. The metabolic syndrome, which is accompanied with sustained hyperinsulinemia, was strongly related to increased risk of colorectal adenomas. Glucose intolerance and high levels of C-peptide, a measure of hyperinsulinemia, were also associated with increased risk of adenomas, but neither IGF-I nor IGFBP-3 was associated with colorectal adenomas. Increased risk of colorectal adenomas associated with hyperglycemia or hyperinsulinemia is probably linked with a mechanism or mechanisms other than the IGF system. A folate-related genetic polymorphism, reportedly associated with colorectal cancer, was not related to colorectal adenomas. Nor was the ALDH2 polymorphism. However, a polymorphism of CYP7A1, an enzyme in the synthesis of bile acids, was associated with right-side colon adenomas, indicating that bile acids is linked with carcinogenesis in the right side colon. Smoking and alcohol use were both related to increased risk of colorectal adenomas, especially of distal adenomas. It was found that coffee was protective against diabetes mellitus, which is an important risk factor for colorectal adenomas. Smoking and alcohol use were related to deterioration in glucose tolerance. A dietary pattern representing high intake of dairy foods and fruits was found not only to be related to decreased risk of colorectal adenomas but also to be protective against glucose tolerance abnormality