title: Dietary calcium, vitamin D, VDR genotypes and colorectal cancer.
abstract: The vitamin D receptor (VDR) may importantly modulate risk of colorectal cancer either independently or in conjunction with calcium and vitamin D intake. We evaluate the association between calcium, vitamin D, dairy products, and VDR polymorphisms in 2 case-control studies of colon and rectal cancer (n = 2,306 cases and 2,749 controls). Dietary intake was evaluated using a detailed diet history questionnaire. Two VDR polymorphisms were evaluated: an intron 8 Bsm 1 polymorphism and a 3' untranslated region poly-A length polymorphism (designated S for short and L for long). The SS genotype reduced risk of colorectal cancer for men (odds ratio [OR] = 0.71; 95% confidence interval [CI] = 0.55-0.92). High levels of calcium intake reduced risk of rectal cancer in women (OR = 0.39; 95% CI = 0.24-0.64) but were not associated with rectal cancer in men (OR = 1.02; 95% CI = 0.66-1.56). Similar reduced rectal cancer risk among women was observed at high levels of vitamin D (OR = 0.52; 95% CI = 0.32-0.85) and low-fat dairy products (OR = 0.61; 95% CI = 0.39-0.94). High levels of sunshine exposure reduced risk of rectal cancer among those diagnosed when <60 years of age (OR = 0.62, 95% CI = 0.42-0.93). Examination of calcium in conjunction with VDR genotype showed that a significant 40% reduction in risk of rectal cancer was observed for the SS or BB VDR genotypes when calcium intake was low (p interaction = 0.01 for calcium interaction). For colon cancer, high levels of dietary intake of calcium, vitamin D, and low-fat dairy products reduced risk of cancer for the SS or BB VDR genotypes, although the p for interaction was not statistically significant. These data support previous observations that high levels of calcium and vitamin D reduce risk of rectal cancer and provide support for a weak protective effect for the SS and BB VDR genotypes. The risk associated with VDR genotype seems to depend upon the level of dietary calcium and vitamin D and tumor site.
authors.affiliation: Health Research Center, University of Utah, Salt Lake City, UT 84108, USA. mslatter@hrc.utah.edu
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Susan L
authors.initials: SL
authors.lastname: Neuhausen
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffman
authors.forename: Bette
authors.initials: B
authors.lastname: Caan
authors.forename: Karen
authors.initials: K
authors.lastname: Curtin
authors.forename: Khe Ni
authors.initials: KN
authors.lastname: Ma
authors.forename: Wade
authors.initials: W
authors.lastname: Samowitz
mesh_terms: D000328:Adult; D000368:Aged; D002136:Calcium, Dietary; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control*; D003611:Dairy Products; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D013472:Sunlight; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D002136:Calcium, Dietary; D018167:Receptors, Calcitriol; D014807:Vitamin D