Vitamin D–Related Genetic Variation, Plasma Vitamin D, and Risk of Lethal Prostate Cancer Full Text
Journal of the National Cancer Institute, 04/13/2012  Clinical Article

Shui IM et al. – In this prospective study, plasma 25(OH)D levels and common variation among several vitamin D–related genes were associated with lethal prostate cancer risk, suggesting that vitamin D is relevant for lethal prostate cancer.

• The authors assessed prediagnostic 25-hydroxyvitamin D [25(OH)D] levels in plasma, variation in vitamin D–related genes, and risk of lethal prostate cancer using a prospective case–control study nested within the Health Professionals Follow-up Study.
• They included 1260 men who were diagnosed with prostate cancer after providing a blood sample in 1993-1995 and 1331 control subjects.
• Men with prostate cancer were followed through March 2011 for lethal outcomes (n=114).
• They selected 97 single-nucleotide polymorphisms (SNPs) in genomic regions with high linkage disequilibrium (tagSNPs) to represent common genetic variation among seven vitamin D–related genes (CYP27A1, CYP2R1, CYP27B1, GC, CYP24A1, RXRA, and VDR).
• They used a logistic kernel machine test to assess whether multimarker SNP sets in seven vitamin D pathway–related genes were collectively associated with prostate cancer.
• Tests for statistical significance were two-sided.

• Higher 25(OH)D levels were associated with a 57% reduction in the risk of lethal prostate cancer (highest vs lowest quartile: odds ratio=0.43, 95% confidence interval=0.24 to 0.76).
• This finding did not vary by time from blood collection to diagnosis.
• They found no statistically significant association of plasma 25(OH)D levels with overall prostate cancer.
• Pathway analyses found that the set of SNPs that included all seven genes (P=.008) as well as sets of SNPs that included VDR (P=.01) and CYP27A1 (P=.02) were associated with risk of lethal prostate cancer.