Murtaugh Maureen A, Sweeney Carol, Ma Khe-Ni, Potter John D, Caan Bette J, Wolff Roger K, Slattery Martha L
Health Research Center, Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT 84108, USA.
Nutr Cancer. 2006;55(1):35-43. doi: 10.1207/s15327914nc5501_5.
Modifiable risk factors in colorectal cancer etiology and their interactions with genetic susceptibility are of particular interest. Functional vitamin D receptor (VDR) gene polymorphisms may influence carcinogenesis through modification of cell growth, protection from oxidative stress, cell-cell matrix effects, or insulin and insulin-like growth factor pathways. We investigated interactions between foods (dairy products, red and processed meat, and whole and refined grains) and dietary patterns (sucrose-to-fiber ratio and glycemic index) associated with insulin resistance with the FokI polymorphism of the VDR gene and colon and rectal cancer risk. Data (diet, anthropometrics, and lifestyle) and DNA came from case-control studies of colon (1,698 cases and 1,861 controls) and rectal cancer (752 cases and 960 controls) in northern California, Utah, and the Twin Cities metropolitan area, Minnesota (colon cancer study only). Unconditional logistic regression models were adjusted for smoking, race, sex, age, body mass index, physical activity, energy intake, dietary fiber, and calcium. The lowest colon cancer risk was observed with the Ff/ff FokI genotypes and a low sucrose-to-fiber ratio. Rectal cancer risk decreased with greater consumption of dairy products and increased with red or processed meat consumption and the FF genotype. Modifiable dietary risk factors may be differentially important among individuals by VDR genotype and may act through the insulin pathway to affect colon cancer risk and through fat, calcium, or other means to influence rectal cancer risk.
结直肠癌病因中的可改变风险因素及其与遗传易感性的相互作用尤其令人关注。功能性维生素D受体（VDR）基因多态性可能通过改变细胞生长、抵御氧化应激、细胞-细胞基质效应或胰岛素及胰岛素样生长因子途径来影响致癌作用。我们研究了与胰岛素抵抗相关的食物（乳制品、红肉和加工肉类以及全谷物和精制谷物）和饮食模式（蔗糖与纤维的比例以及血糖指数）与VDR基因的FokI多态性及结肠癌和直肠癌风险之间的相互作用。数据（饮食、人体测量学和生活方式）和DNA来自加利福尼亚北部、犹他州以及明尼苏达州双子城大都市地区的结肠癌（1698例病例和1861例对照）和直肠癌（752例病例和960例对照）病例对照研究（仅结肠癌研究）。无条件逻辑回归模型针对吸烟、种族、性别、年龄、体重指数、身体活动、能量摄入、膳食纤维和钙进行了调整。Ff/ff FokI基因型且蔗糖与纤维比例低时观察到最低的结肠癌风险。直肠癌风险随着乳制品摄入量的增加而降低，随着红肉或加工肉类摄入量的增加以及FF基因型而增加。可改变的饮食风险因素在不同VDR基因型个体中可能具有不同的重要性，并且可能通过胰岛素途径影响结肠癌风险，通过脂肪、钙或其他方式影响直肠癌风险。
