Sex steroid hormone metabolism in relation to risk of aggressive prostate cancer
Couplée aux données de la cohorte "Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial" et portant sur 195 cas et 195 témoins, cette étude américaine évalue l'association entre le niveau sérique d'hormones sexuelles stéroïdiennes et le risque de cancer aggressif de la prostate
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.