Abstract B07: Ratio of plasma 1,25(OH)2D to 25(OH)D is inversely associated with aggressive prostate cancer in African Americans in the North Carolina-Louisiana Prostate Cancer Project (PCaP)
Authors: Steck Susan E. , Woloszynska-Read Anna , Arab Lenore , McMahon Daria , Bensen Jeannette , Adams John S. , Fontham Elizabeth T.H. , Mohler James L. , Su L. Joseph , Zhang Hongmei , Trump Donald , Johnson Candace 
Published: May 2015

Introduction: Epidemiologic studies have reported conflicting results when examining the relationship between circulating vitamin D metabolites and risk of advanced prostate cancer. While 25-hydroxy vitamin D [25(OH)D] is used as a measure of vitamin D status, 1,25-dihydroxy vitamin D [1,25(OH)2D] is the biologically active form and its concentration is tightly regulated. We previously reported increased odds of aggressive prostate cancer among African Americans in the highest tertile of plasma 25(OH)D compared to the lowest, and have now examined plasma 1,25(OH)2D and the ratio of 1,25(OH)2D to 25(OH)D in relation to prostate cancer aggressiveness.

Methods: Plasma 1,25(OH)2D and 25(OH)D were measured using LC/MS/MS in 435 African-American and 563 European-American men with newly-diagnosed prostate cancer from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Men were classified as highly aggressive cases at time of diagnosis if Gleason sum ≥8, or PSA &gt;20 ng/ml, or Gleason sum ≥7 AND clinical stage = T3-T4, or Gleason sum=7 with a pattern of (4+3). The comparison group (low aggressiveness) included men with Gleason sum &lt;7 AND Stage T1-T2 AND PSA &lt; 9 ng/ml. Plasma 1,25(OH)2D and the ratio of plasma 1,25(OH)2D to 25(OH)D were categorized into tertiles and quartiles, respectively, based on distributions among low aggressive research subjects in each race separately. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated for high aggressive prostate cancer by tertiles of 1,25(OH)2D or quartiles of the 1,25(OH)2D:25(OH)D ratio using logistic regression with adjustment for potential confounders.

Results: Plasma 1,25(OH)2D was not associated with odds of aggressive prostate cancer in either African Americans or European Americans in this study (OR=0.83, 95%CI=0.49, 1.41 and OR=0.67, 95%CI=0.40, 1.11, respectively, for highest tertile compared to lowest tertile). However, higher quartiles (as compared to the lowest quartile) of 1,25(OH)2D:25(OH)D ratio were associated with reduced odds of high aggressive disease among African Americans after adjustment for age, season, education, alcohol intake, smoking status, PSA screening history, physical activity, energy intake, use of non-steroidal anti-inflammatory drugs, study site and body mass index (OR=0.51, 95%CI=0.28, 0.91; OR=0.41, 95%CI=0.22, 0.76, and OR=0.46, 95%CI=0.25, 0.84 for 2nd, 3rd and 4th quartiles, respectively). Inverse associations were also observed for European Americans, but were not statistically significant (OR=0.64, 95%CI=0.35, 1.17 for 4th compared to 1st quartile).

Conclusions: The ratio of plasma 1,25(OH)2D to 25(OH)D was inversely associated with prostate cancer aggressiveness among African Americans. Blood samples were collected after diagnosis, thus, it is possible that effects of treatment or extent of disease or associated processes (e.g., weight loss) on plasma vitamin D metabolites may have affected their measurement. Future analyses in PCaP will include examining circulating parathyroid hormone, calcium and phosphorus, as well as genotyping of genes encoding enzymes involved in the vitamin D metabolism and activity, which may help to explain these findings.

Citation Format: Susan E. Steck, Anna Woloszynska-Read, Lenore Arab, Daria McMahon, Jeannette Bensen, John S. Adams, Elizabeth T.H. Fontham, James L. Mohler, L. Joseph Su, Hongmei Zhang, Donald Trump, Candace Johnson. Ratio of plasma 1,25(OH)2D to 25(OH)D is inversely associated with aggressive prostate cancer in African Americans in the North Carolina-Louisiana Prostate Cancer Project (PCaP). [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B07. doi:10.1158/1538-7755.DISP13-B07