Abstract 5069: Circulating 25-hydroxyvitamin D and prostate cancer survival

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Basic research suggests that vitamin D may inhibit prostate tumorigenesis through a number of mechanisms, including enhanced cellular differentiation and apoptosis, but epidemiological studies do not indicate an inverse circulating vitamin D-prostate cancer risk association. However, low circulating 25-hydroxyvitamin D [25(OH)D] concentrations, the accepted biomarker of vitamin D status, have been associated with reduced prostate cancer survival. Methods: We examined circulating 25(OH)D in relation to prostate cancer survival in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish men. Among 1,000 participants diagnosed with prostate cancer through April 2005, 359 had died, with mortality follow-up through December 2012. 25(OH)D was measured in fasting serum samples prospectively drawn at the study baseline, using the DiaSorin LIAISON 25(OH)D TOTAL assay, with interbatch and intrabatch CVs of 12.3% and 10.5%, respectively. Age-adjusted proportional hazard regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between 25(OH)D and survival, based on season-specific quartiles of vitamin D (cutpoints were: Q1 18 and 28 and 42 nmol/L for the less sunny months; Q1 29 and 42 and 56 nmol/L for sunnier months). Results: Median time from fasting blood collection to prostate cancer diagnosis was 12.6 years (range < 1 year-19.6 years), and median survival time among men who died of prostate cancer was 3.2 years (range 0-18.9 years). For cases still alive at the end of the follow-up period, median follow-up time was 7.8 years (range 0-22 years). Serum 25(OH)D did not differ between the men who died during follow-up and those who remained alive (medians 37.4 and 38.4 nmol/L, respectively; p=0.37). Men with higher baseline concentrations were at reduced risk of death compared with men at the lowest 25(OH)D quartile, however: for quartiles 2-4, HR 0.73 (95% CI 0.54-0.97), HR 0.55 (0.41-0.74), and HR 0.67 (0.50-0.90), respectively; p-trend = 0.003). The prostate cancer mortality reduction was observed primarily among non-advanced cases diagnosed within 12 years of blood collection (stage 1-2 or Gleason <8; Q4 HR 0.25 (95% CI 0.09-0.74), with weaker, non-significant associations for advanced cases diagnosed within that time frame (Q4 HR 0.80) and for non-advanced cases diagnosed after longer (12+ years) follow-up (Q4 HR 0.82), and no association among advanced cases diagnosed after longer follow-up (Q4 HR 0.99). Conclusion: In this prospective cohort study with blood drawn prior to cancer diagnoses, higher serum 25(OH)D concentrations were associated with increased prostate cancer survival. How higher vitamin D status improves survival, particularly in the context of having been related to elevated risk of developing prostate cancer in the same cohort, will require further study. Citation Format: Stephanie J. Weinstein, Alison Mondul, Satu Mannisto, Demetrius Albanes. Circulating 25-hydroxyvitamin D and prostate cancer survival. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5069. doi:10.1158/1538-7445.AM2014-5069