Case-control study of vitamin D, dickkopf homolog 1 (DKK1) gene methylation, VDR gene polymorphism and the risk of colon adenoma in African Americans.
BACKGROUND
There are sparse data on genetic, epigenetic and vitamin D exposure in African Americans (AA) with colon polyp. Consequently, we evaluated serum 25(OH) D levels, vitamin D receptor (VDR) polymorphisms and the methylation status of the tumor suppressor gene dickkopf homolog 1 (DKK1) as risk factors for colon polyp in this population.


METHODS
The case-control study consisted of 93 patients with colon polyp (cases) and 187 healthy individuals (controls) at Howard University Hospital. Serum levels of 25(OH)D (including D3, D2, and total) were measured by liquid chromatography-mass spectrometry. DNA analysis focused on 49 single nucleotide polymorphisms (SNPs) in the VDR gene. Promoter methylation analysis of DKK1 was also performed. The resulting data were processed in unadjusted and multivariable logistic regression analyses.


RESULTS
Cases and controls differed in vitamin D status (D(3)<50 nmol/L: Median of 35.5 in cases vs. 36.8 in controls nmol/L; P = 0.05). Low levels of 25(OH)D(3) (<50 nmol/L) were observed in 86% of cases and 68% of controls and it was associated with higher risks of colon polyp (odds ratio of 2.7, 95% confidence interval 1.3-3.4). The SNP analysis showed no association between 46 VDR polymorphisms and colon polyp. The promoter of the DKK1 gene was unmethylated in 96% of the samples.


CONCLUSIONS
We found an inverse association between serum 25(OH)D(3) and colon polyp in AAs. VDR SNPs and DKK1 methylation were not associated with colon polyp. Vitamin D levels may in part explain the higher incidence of polyp in AAs.
Department of Medicine and Cancer Center, College of Medicine, Howard University, Washington, DC, United States of America. hashktorab@howard.edu
Hassan
H
Ashktorab
Bijou
B
Nguza
Mehrnaz
M
Fatemi
Mehdi
M
Nouraie
Duane T
DT
Smoot
Alejandro A
AA
Schäffer
Sonia S
SS
Kupfer
Carlos A
CA
Camargo
Hassan
H
Brim
D000236:Adenoma / Q000097:blood / Q000235:genetics; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000097:blood / Q000235:genetics; D003111:Colonic Polyps / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D012621:Seasons; D014807:Vitamin D / Q000097:blood*
C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D018167:Receptors, Calcitriol; D014807:Vitamin D