Sequence variation within the 5' regulatory regions of the vitamin D binding protein and receptor genes and prostate cancer risk.
BACKGROUND
The vitamin D receptor (VDR) and binding protein (DBP) mediate the cellular transport, activity, and anti-tumor action of 1,25-dihydroxyvitamin D3 [1,25-(OH)(2)D3]. The purpose of this investigation is to determine whether novel single nucleotide polymorphisms (SNPs) within the transcriptional regulatory regions of the VDR and DBP are associated with prostate cancer risk.


METHODS
Novel SNPs were identified in the VDR and DBP transcription regulatory gene regions and genotyped in a case-control study using male subjects with (n=258) or without (n=434) prostate cancer.


RESULTS
African-American men who possessed at least one variant VDR-5132 C allele had a increased risk of prostate cancer (OR=1.83; 95% CI: 1.02, 3.31). Further study revealed that the VDR-5132 T/C SNP eliminates a GATA-1 transcription factor-binding site.


CONCLUSIONS
The VDR-5132 T/C SNP, resulting in potential elimination of the GATA-1 transcription factor-binding site, may increase prostate cancer susceptibility in African-Americans. Confirmation of these findings is needed in larger observational studies.
Kidd
La Creis R
LC
Department of Pharmacology and Toxicology, Cancer Prevention and Control Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky.
Paltoo
Dina N
DN
Wang
Songping
S
Chen
Weidong
W
Akereyeni
Folasade
F
Isaacs
William
W
Ahaghotu
Chiledum
C
Kittles
Rick
R
D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D014809:Vitamin D-Binding Protein / Q000235:genetics*; D044465:White People / Q000235:genetics
D020121:5' Untranslated Regions; D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein