Stephanie Weinstein

Ph.D

NCI

Staff Scientist

PLCO (Learn more about this study)

PLCO-113

Nov 19, 2014

Influence of circulating testosterone concentrations on the relationship between 25(OH)D and prostate cancer

Emerging data indicate that while circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, is associated with reduced risk of colorectal and possibly other cancers, higher 25(OH)D concentrations appear related to increased prostate cancer risk. Published data from PLCO (Ahn et al, JNCI 2007) report an increased risk of aggressive prostate cancer with higher concentrations of 25(OH)D. More recently, our group has also reported an increased risk of prostate cancer with higher concentrations of 25(OH)D (Albanes et al, CEBP 2011), an association that appeared modified by circulating vitamin D binding protein (DBP) concentrations such that the elevated risk for higher 25(OH)D is stronger when DBP concentrations are above the median (Weinstein et al, IJC 2012). One potential mechanism we hypothesized for this effect modification is that higher extracellular concentrations of DBP plus 25(OH)D result in up-regulation of megalin-mediated internalization of not only the DBP-25(OH)D complex but also SHBG-bound testosterone, thereby providing a direct androgenic stimulus for prostate tumor progression and growth.
In order to test this hypothesis, we request existing sex hormone, serum vitamin D, and DBP data from PLCO to conduct a nested case-control study of prostate cancer and examine their possible interactions.

• Test whether the association between circulating 25(OH)D and prostate cancer is confounded or modified by circulating hormone concentrations (testosterone, dihydrotestosterone, androstanediol, androstendione, and sex hormone binding globulin)

• Test whether these associations are further modified by circulating DBP concentrations.