Vitamin D receptor gene polymorphisms, dietary promotion of insulin resistance, and colon and rectal cancer.
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.
Murtaugh
Maureen A
MA
Health Research Center, Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT 84108, USA. maureen.murtaugh@hsc.utah.edu
Sweeney
Carol
C
Ma
Khe-Ni
KN
Potter
John D
JD
Caan
Bette J
BJ
Wolff
Roger K
RK
Slattery
Martha L
ML
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D003611:Dairy Products; D004032:Diet; D004043:Dietary Fiber / Q000008:administration & dosage; D019422:Dietary Sucrose / Q000008:administration & dosage; D002523:Edible Grain; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D038321:Glycemic Index; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D016015:Logistic Models; D008297:Male; D008461:Meat Products; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D012004:Rectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
D004043:Dietary Fiber; D019422:Dietary Sucrose; D007328:Insulin; D018167:Receptors, Calcitriol