Abstract Background: In an effort to understand the molecular mechanism behind the association between circulating vitamin D and prostate cancer, we measured relative telomere length and 25(OH)D levels in a cohort of older Finnish men. Methods: Using a nested study design, we examined quantitative PCR measured telomere length, season-adjusted serum 25-hydroxyvitamin D [25(OH)D], and subsequent prostate cancer risk in 1000 men (n=500 cases, 500 matched controls) participating in the extension study of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Trial. Conditional regression models were used to explore mediation and effect modification of telomere length on the relation between serum 25(OH)D and prostate cancer risk. Results: An increased risk of prostate cancer was observed among men with longer (>median) relative telomere length (OR = 1.41, 95% CI: 1.06 to 1.90; continuous: OR = 2.36, 95%CI: 0.96 to 5.83) as well as men with higher 25(OH)D concentrations (OR = 1.67, 95% CI: 1.08 to 2.57 for highest vs. lowest quintile, P-trend = 0.03). No significant association between 25(OH)D levels and telomere length was observed. A suggested joint effect of 25(OH)D and telomere length on prostate cancer risk was observed. Conclusion: Serum 25(OH)D and relative telomere length are independent predictors of prostate cancer risk in this sample of older male Finnish smokers. No evidence of mediation between circulating vitamin D concentrations and telomere length was observed. Future studies are needed to further clarify the underlying biologic mechanisms of the 25(OH)D-prostate cancer association. Citation Format: Jacqueline M. Major, Barry I. Graubard, Stephanie J. Weinstein, Jeeyun Kim, Immaculata De Vivo, Jarmo Virtamo, Sharon A. Savage, Demetrius Albanes. Understanding the mechanism underlying vitamin D and prostate cancer: Exploring telomere length [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-172.
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