Vitamin D Pathway and Other Related Polymorphisms and Risk of Prostate Cancer: Results from the Prostate Cancer Prevention Trial.

Abstract

Vitamin D may influence prostate cancer risk, but evidence is inconsistent. We conducted a nested case-control study in the Prostate Cancer Prevention Trial (PCPT). Cases (n = 1,128) and controls (n = 1,205) were frequency matched on age, first-degree relative with prostate cancer, and PCPT treatment arm (finasteride/placebo); African-Americans were oversampled and case/control status was biopsy confirmed. We selected 21 SNPs in vitamin D-related genes (VDR, GC, C10orf88, CYP2R1, CYP24A1, CYP27B1, DHCR7, and NADSYN1) to test genotype and genotype-treatment interactions in relation to prostate cancer. We also tested mean serum 25(OH)D differences by minor allele distributions and tested for serum 25(OH)D-genotype interactions in relation to prostate cancer risk. Log-additive genetic models (Bonferroni-corrected within genes) adjusted for age, body mass index, PSA, and family history of prostate cancer revealed a significant interaction between treatment arm and GC/rs222016 (finasteride OR = 1.37, placebo OR = 0.85; P interaction < 0.05), GC/rs222014 (finasteride OR = 1.36, placebo OR = 0.85; P interaction < 0.05), and CYP27B1/rs703842 (finasteride OR = 0.76, placebo OR = 1.10; P interaction < 0.05) among Caucasians, and C10orf88/rs6599638 (finasteride OR = 4.68, placebo OR = 1.39; P interaction < 0.05) among African-Americans. VDR/rs1544410 and CYP27B1/rs703842 had significant treatment interactions for high-grade disease among Caucasians (finasteride OR = 0.81, placebo OR = 1.40; P interaction < 0.05 and finasteride OR = 0.70, placebo OR = 1.28; P interaction < 0.05, respectively). Vitamin D-related SNPs influenced serum 25(OH)D, but gene-serum 25(OH)D effect modification for prostate cancer was marginally observed only for CYP24A1/rs2248359. In conclusion, evidence that vitamin D-related genes or gene-serum 25(OH)D associations influence prostate cancer risk is modest. We found some evidence for gene-finasteride interaction effects for prostate cancer in Caucasians and African-Americans. Results suggest only minimal associations of vitamin D with total or high-grade prostate cancer.

• Authors: Kathleen Torkko, Cathee Till, Catherine M Tangen, Phyllis J Goodman, Xiaoling Song, Jeannette M Schenk, M Scott Lucia, Ulrike Peters, Adrie van Bokhoven, Ian M Thompson, Marian L Neuhouser
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 13 Issue 6 Pg. 521-530 (06 2020) ISSN: 1940-6215 [Electronic] United States
• PMID: 32102946 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• 5-alpha Reductase Inhibitors
• Vitamin D
• Finasteride
• 25-hydroxyvitamin D
• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
• CYP27B1 protein, human

Topics

• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (genetics)
• 5-alpha Reductase Inhibitors (therapeutic use)
• Adenocarcinoma (epidemiology, genetics, prevention & control)
• Black or African American (genetics)
• Aged
• Aged, 80 and over
• Case-Control Studies
• Finasteride (therapeutic use)
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• Metabolic Networks and Pathways (genetics)
• Middle Aged
• Polymorphism, Single Nucleotide
• Prostatic Neoplasms (epidemiology, genetics, prevention & control)
• Randomized Controlled Trials as Topic (statistics & numerical data)
• Risk
• Vitamin D (analogs & derivatives, blood, metabolism)
• White People (genetics)