MP07-05 SERUM TESTOSTERONE AS A BIOMARKER FOR PROSTATE CANCER DIAGNOSIS IN THE IMPACT POPULATION

Abstract

INTRODUCTION AND OBJECTIVES: The relation of serum androgens and the development of prostate cancer (PCa) is subject of debate. Lower total testosterone (TT) levels have been associated with increased PCa detection and worse pathological features after treatment. The aim of this study is to investigate the association of serum androgens levels and PCa detection in a prospective screening study of men at higher genetic risk due to BRCA mutation METHODS: Six hundred and fifty seven participants in the IMPACT study had sequential TT and sexual hormone binding globulin (SHBG) measurements in serum samples at annual visits, giving 2783 prospective androgen levels, from 234 BRCA1 carriers, 268 BRCA2 carriers and 155 mutation negative controls. Free and bioavailable testosterone were calculated from TT and SHBG using the Sordergaard equation. Age, BMI, PSA and hormonal concentrations were compared between men affected and unaffected with PCa within each genetic cohort using unpaired t-test. The Fisher exact test was used to correlate hypogonadic levels of testosterone and genetic status with PCa diagnosis within each genetic category RESULTS: There were no significant differences in the PSA levels and BMI at study entry. Mean ages were 53.52, 52.17, and 51.17 years, for the control, BRCA1 and BRCA2 groups, respectively (BRCA1 p1⁄40.24 and BRCA2 p1⁄40.01). In the BRCA2 cohort, serum TT levels were lower in carriers diagnosed with PCa, compared with unaffected carriers and controls (11.2, 13.78, 13.4 nmol/L, mean values per group, respectively, p1⁄40.02 and p1⁄40.009). In the BRCA1 cohort, no significant difference was observed between affected and unaffected carriers and controls (13.6, 13.5, 13.4, nmol/L, mean values per group respectively, p1⁄40.82 and p-0.69). SHBG levels were significantly higher in BRCA1 carriers with PCa than unaffected carriers and controls (47.62, 37.97, 40.34 nmol/L, respectively; p1⁄40.002 and p1⁄40.03). TT levels <8nmol/L were significantly more frequent among BRCA2 carriers with PCa then unaffected carriers and controls (OR 2.78, 95% CI: 1.3-5.8, p1⁄40.01). This finding was not observed in the BRCA1 cohort. There was no significant difference in the levels of free and bioavailable testosterone in both cohorts CONCLUSIONS: Our findings indicate that there is a difference between BRCA1 and BRCA2 carriers who develop PCa in relation to serumTT and SHBG levels. BRCA2 carriers affected with PCa had lower total testosterone levels, and affected BRCA1 carriers had higher levels of SHBG. These data are preliminary but may indicate that these values could be explored as biomarkers for BRCA-related prostate cancer