Background: The combined action of androgens and estrogens-specifically their balance-may play a role in prostate carcinogenesis but existing evidence is sparse and inconsistent.
We investigated associations between serum sex steroid hormones, including estrogen metabolites, and risk of aggressive prostate cancer.
Methods: In a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort we measured serum estrone, estradiol and 13 estrogen metabolites, in the 2-, 4, or 16-hydroxylation pathways, using a liquid chromatography-tandem mass spectrometry assay. Cases (n=195) were non-Hispanic white men aged 55-70 years when diagnosed with aggressive prostate cancer (stage III or IV and/or Gleason ≥7). Controls (n=195) were non-Hispanic white men without prostate cancer who were frequency-matched to cases by age and year at blood draw, time since baseline screen. Only men with serum testosterone and sex hormone-binding globulin measured previously were eligible. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI).
Results: Risk of aggressive prostate cancer was strongly inversely associated with estradiol:testosterone ratio (OR4th quartile vs. 1st =0.27, 95% CI 0.12-0.59, p trend=0.003) and positively associated with 2:16α-hydroxyestrone ratio (OR4th quartile vs. 1st =2.44, 95% CI 1.34-4.45, p trend=0.001). Estradiol, estrone and estrogen metabolites were unrelated to risk.
Conclusions: Our findings suggest that sex steroid hormones, specifically the estrogen-androgen balance, may be important in the development of aggressive prostate cancer.
Impact: Improved understanding of the hormonal etiology of prostate cancer is critical for prevention and therapeutic interventions.
Black A, Pinsky PF, Grubb RL 3rd, Falk RT, Hsing AW, Chu L, Meyer T, Veenstra TD, Xu X, Yu K, Ziegler RG, Brinton LA, Hoover RN, Cook MB. Are you the author?
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health; Division of Urology, Washington University School of Medicine; Division of Cancer Epidemiology and Genetics, Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, National Institutes of Health; Department of Research, Cancer Prevention Institute of California; Pharmacovigilance Center, U.S. Army Medical Command, Surgeon General of the Army; C2N Diagnostics; Laboratory of Proteomics and Analytic Technologies, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research.
Reference: Cancer Epidemiol Biomarkers Prev. 2014 Sep 1. pii: cebp.0700.2014.