Risk of Early-Onset Prostate Cancer in Relation to Germ Line Polymorphisms of the Vitamin D Receptor

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 13; no. 8; pp. 1325 - 1330
• Main Authors: OAKLEY-GIRVAN, Ingrid, FELDMAN, David, WHITTEMORE, Alice S, ECCLESHALL, T. Ross, GALLAGHER, Richard P, WU, Anna H, KOLONEL, Laurence N, HALPERN, Jerry, BALISE, Raymond R, WEST, Dee W, PAFFENBARGER, Ralph S
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.2004
• Subjects: Adult; African Americans - genetics; Age Distribution; Age of Onset; Aged; Biological and medical sciences; Case-Control Studies; Confidence Intervals; European Continental Ancestry Group - genetics; Genetic Predisposition to Disease; Germinoma - ethnology; Germinoma - genetics; Humans; Incidence; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Odds Ratio; Polymorphism, Genetic; Prognosis; Prostatic Neoplasms - ethnology; Prostatic Neoplasms - genetics; Receptors, Calcitriol - genetics; Reference Values; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; United States; North America; America; Human; Urinary system disease; Genetic variability; Prostate disease; Family study; Genotype; Malignant tumor; Epidemiology; Age of onset; Vitamin D; Germ line; Risk factor; Genetics; Early; Male genital diseases; Prostate cancer; Public health; Biological receptor
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.1325.13.8

Vitamin D inhibits prostate cancer cell growth, angiogenesis, and metastasis. These actions are mediated by the vitamin D receptor. We examined associations between prostate cancer risk and five polymorphisms in the VDR gene: four single nucleotide polymorphisms ( Fok I, Bsm I, Apa I, and Taq I restriction sites) and the polyadenylic acid microsatellite. Specifically, we genotyped population-based samples of young African Americans (113 cases and 121 controls) and Whites (232 cases and 171 controls) and members of 98 predominantly White families with multiple cases of prostate cancer. Among Whites, there was no evidence for association between prostate cancer risk and alleles at any of the five polymorphic sites regardless of how the men were ascertained. Moreover, estimated five-locus haplotype frequencies were similar in White cases and controls. Among African Americans, prostate cancer risk was associated with homozygosity for the F allele at the Fok I site (odds ratio 1.9, 95% confidence interval 1.0-3.3). In addition, estimated haplotype frequencies differed significantly ( P < 0.01) between African American cases and controls. These findings need replication in other studies of African Americans. Homozygosity for the F allele at the Fok I site is more prevalent in the African American population than in U.S. Whites. If the Fok I association noted here were causal, this difference could account for some of the disease burden among African Americans and some of the excess risk in African Americans compared with Whites.