Association of vitamin D receptor gene variants, adiposity and colon cancer

Carcinogenesis. 2008 Sep;29(9):1788-93. doi: 10.1093/carcin/bgn166. Epub 2008 Jul 14.

Abstract

Vitamin D receptor (VDR) gene variants have been variably associated with risk of colon cancer in epidemiologic studies. We sought to further clarify the relationship between colon cancer and three single-nucleotide polymorphisms (SNPs) in the VDR gene (Cdx-2, FokI and TaqI) in a population-based case-control study of 250 incident cases and 246 controls. Colon cancer cases were more frequently homozygous for the Cdx-2 A allele (9.2 versus 4.1%, P = 0.06). Cdx-2 AA homozygotes were at increased risk with an unadjusted odds ratio (OR) of 2.47 [95% confidence interval (CI): 1.13-5.37, P = 0.022]; adjustment for age, sex, body mass index (BMI), non-steroidal anti-inflammatory use and family history of colorectal cancer yielded an OR of 2.27 (CI: 0.95-5.41, P = 0.065). Carriers of the FokI TT genotype were also at increased risk with an adjusted OR of 1.87 (CI: 1.03-3.38, P = 0.038). Haplotype analyses showed significant increased colon cancer risk for carriers of the Cdx-2-FokI A-T haplotype and the FokI-TaqI T-G haplotype. The three-SNP Cdx-2-FokI-TaqI (A-T-G) haplotype showed a similar association with an adjusted OR of 3.63 (CI: 1.01-13.07). A strong positive association was observed for the Cdx-2 variant among individuals with low BMI or low waist circumference. Our results suggest that genetic variation at the VDR locus, in particular Cdx-2 and FokI SNPs, may influence colon cancer risk and these associations may be modified by adiposity.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index
  • CDX2 Transcription Factor
  • Case-Control Studies
  • Colonic Neoplasms / epidemiology
  • Colonic Neoplasms / genetics*
  • Female
  • Genetic Linkage
  • Genetic Predisposition to Disease
  • Haplotypes / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Male
  • Middle Aged
  • Obesity / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Calcitriol / genetics*
  • Risk Factors
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) / genetics
  • Taq Polymerase / genetics
  • Trans-Activators / genetics
  • Vitamin D / metabolism

Substances

  • CDX2 Transcription Factor
  • Homeodomain Proteins
  • Receptors, Calcitriol
  • Trans-Activators
  • Vitamin D
  • DNA modification methylase FokI
  • Site-Specific DNA-Methyltransferase (Adenine-Specific)
  • Taq Polymerase