Dietary calcium, vitamin D, VDR genotypes and colorectal cancer

Int J Cancer. 2004 Sep 20;111(5):750-6. doi: 10.1002/ijc.20330.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Calcium, Dietary*
  • Case-Control Studies
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / physiopathology
  • Colorectal Neoplasms / prevention & control*
  • Dairy Products
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, Calcitriol / genetics*
  • Risk Factors
  • Sunlight
  • Vitamin D / pharmacology*


  • Calcium, Dietary
  • Receptors, Calcitriol
  • Vitamin D