Carcinogenesis Advance Access originally published online on July 14, 2008
Carcinogenesis 2008 29(9):1788-1793; doi:10.1093/carcin/bgn166
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Association of vitamin D receptor gene variants, adiposity and colon cancer
1 Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, USA
2 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
3 Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA
4 Department of Family Medicine, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, OH, USA
5 Case Center for Transdisciplinary Research on Energetics and Cancer, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA
6 Cancer Control Program, University of Kentucky, Lexington, KY, USA
7 Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
8 Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
* To whom correspondence should be addressed. Research Division, Department of Family Medicine, Case Western Reserve University, 11001 Cedar Avenue, Suite 306, Cleveland, OH 44106-7136, USA. Tel: +1 216 368 5437; Fax: +1 216 368 4348; Email: lxl62{at}cwru.edu
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.
Abbreviations: BMI, body mass index; CI, confidence interval; HWE, Hardy–Weinberg equilibrium; LD, linkage disequilibrium; MAF, minor allele frequency; (25(OH)D), 25-hydroxyvitamin D; OR, odds ratio; PCR, polymerase chain reaction; SNP, single nucleotide polymorphism; VDR, vitamin D receptor
Received March 27, 2008; revised July 8, 2008; accepted July 9, 2008.
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