Association of vitamin D receptor gene variants, adiposity and colon cancer.
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.
Ochs-Balcom
Heather M
HM
Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, USA.
Cicek
Mine S
MS
Thompson
Cheryl L
CL
Tucker
Thomas C
TC
Elston
Robert C
RC
J Plummer
Sarah
S
Casey
Graham
G
Li
Li
L
D050154:Adiposity / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D000071616:CDX2 Transcription Factor; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics; D019914:Taq Polymerase / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014807:Vitamin D / Q000378:metabolism
D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D018167:Receptors, Calcitriol; D015534:Trans-Activators; D014807:Vitamin D; C058668:DNA modification methylase FokI; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D019914:Taq Polymerase