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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; Pinteraction < 0.05), GC/rs222014 (finasteride OR = 1.36, placebo OR = 0.85; Pinteraction < 0.05), and CYP27B1/rs703842 (finasteride OR = 0.76, placebo OR = 1.10; Pinteraction < 0.05) among Caucasians, and C10orf88/rs6599638 (finasteride OR = 4.68, placebo OR = 1.39; Pinteraction < 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; Pinteraction < 0.05 and finasteride OR = 0.70, placebo OR = 1.28; Pinteraction < 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.
Footnotes
Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).
Cancer Prev Res 2020;13:521–30
- Received August 29, 2019.
- Revision received January 2, 2020.
- Accepted February 20, 2020.
- Published first February 26, 2020.
- ©2020 American Association for Cancer Research.
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