Vitamin D gene pathway polymorphisms and risk of colorectal, breast, and prostate cancer.
Higher vitamin D exposure is hypothesized to prevent several cancers, possibly through genomic effects modulated by the vitamin D receptor (VDR), and autocrine/paracrine metabolism of the VDR's ligand, 1alpha,25-(OH)(2)-vitamin D. Herein we review the background and evidence to date on associations between polymorphisms in VDR and selected genes in the vitamin D pathway in relation to colorectal, breast, and prostate cancer. Although most studies to date have examined only a few VDR polymorphisms, more are beginning to comprehensively investigate polymorphisms in the VDR as well as in other vitamin D pathway genes, such as the vitamin D-binding protein gene (Gc) and CYP27B1 and CYP24A1, which code for enzymes that, respectively, synthesize and degrade 1alpha,25-(OH)(2)-vitamin D. Currently, there is no strong, consistent epidemiologic evidence for substantial influences of single variants in vitamin D pathway genes on risk for colorectal, breast, or prostate cancer, but promising leads are developing.
McCullough
Marjorie L
ML
Department of Epidemiology, American Cancer Society, Atlanta, GA 30303, USA. marji.mccullough@cancer.org
Bostick
Roberd M
RM
Mayo
Tinisha L
TL
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism; D014809:Vitamin D-Binding Protein / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase