Title | Pre-diagnostic circulating sex hormone levels and risk of prostate cancer by ERG tumour protein expression. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Graff RE, Meisner A, Ahearn TU, Fiorentino M, Loda M, Giovannucci EL, Mucci LA, Pettersson A |
Journal | Br J Cancer |
Volume | 114 |
Issue | 8 |
Pagination | 939-44 |
Date Published | 2016 Apr 12 |
ISSN | 1532-1827 |
Keywords | Case-Control Studies, Estradiol, Follow-Up Studies, Gonadal Steroid Hormones, Humans, Immunohistochemistry, Logistic Models, Male, Middle Aged, Odds Ratio, Prospective Studies, Prostatic Neoplasms, Receptors, Androgen, Risk, Serine Endopeptidases, Testosterone, Trans-Activators, Transcriptional Regulator ERG |
Abstract | BACKGROUND: Experimental studies have shown androgen receptor stimulation to facilitate formation of the TMPRSS2:ERG gene fusion in prostate cell lines. No study has tested whether higher pre-diagnostic circulating sex hormone levels in men increase risk of developing TMPRSS2:ERG-positive prostate cancer specifically. METHODS: We conducted a nested case-control study of 200 prostate cancer cases and 1057 controls from the Physicians' Health Study and Health Professionals Follow-up Study. We examined associations between pre-diagnostic circulating levels of total testosterone, free testosterone, DHT, androstanediol glucuronide, estradiol, and SHBG and risk of prostate cancer by TMPRSS2:ERG status. TMPRSS2:ERG was estimated by ERG immunohistochemistry. We used multivariable unconditional polytomous logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of ERG-positive (n=94) and, separately, ERG-negative (n=106) disease. RESULTS: Free testosterone was significantly associated with the risk of ERG-positive prostate cancer (OR: 1.37, 95% CI: 1.05-1.77), but not ERG-negative prostate cancer (OR: 1.09, 95% CI: 0.86-1.38) (Pdiff=0.17). None of the remaining hormones evaluated showed clear differential associations with ERG-positive vs ERG-negative disease. CONCLUSIONS: These findings provide some suggestive evidence that higher pre-diagnostic free testosterone levels are associated with an increased risk of developing TMPRSS2:ERG-positive prostate cancer. |
DOI | 10.1038/bjc.2016.61 |
Alternate Journal | Br J Cancer |
PubMed ID | 26986253 |
PubMed Central ID | PMC4984801 |
Grant List | P50 CA090381 / CA / NCI NIH HHS / United States CA136578 / CA / NCI NIH HHS / United States P01 CA087969 / CA / NCI NIH HHS / United States P01 CA055075 / CA / NCI NIH HHS / United States CA141298 / CA / NCI NIH HHS / United States R01 HL034595 / HL / NHLBI NIH HHS / United States R25 CA112355 / CA / NCI NIH HHS / United States UM1CA167552 / CA / NCI NIH HHS / United States CA097193 / CA / NCI NIH HHS / United States T32 CA09001 / CA / NCI NIH HHS / United States U01 CA098233 / CA / NCI NIH HHS / United States R01 HL026490 / HL / NHLBI NIH HHS / United States T32 CA009001 / CA / NCI NIH HHS / United States UM1 CA167552 / CA / NCI NIH HHS / United States R01 CA040360 / CA / NCI NIH HHS / United States R01 CA136578 / CA / NCI NIH HHS / United States R01 CA097193 / CA / NCI NIH HHS / United States U01CA098233 / CA / NCI NIH HHS / United States CA40360 / CA / NCI NIH HHS / United States R01 CA034944 / CA / NCI NIH HHS / United States R01 CA141298 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.