Sex Steroid Hormone Metabolism in Relation to Risk of Aggressive Prostate Cancer

Abstract

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 an LC/MS-MS assay. Cases (n ¼ 195) were non-Hispanic white men ages 55 to 70 years when diagnosed with aggressive prostate cancer (stage III or IV and/or Gleason !7). Controls (n ¼ 195) were non-Hispanic white men without prostate cancer who were frequency matched to cases by age and year at blood draw, and time since baseline screen. Only men with serum testosterone and sex hormonebinding globulin measured previously were eligible. Logistic regression models were used to estimate ORs and 95% confidence intervals (95% CI).Results: Risk of aggressive prostate cancer was strongly inversely associated with estradiol:testosterone ratio (OR 4th quartile vs. 1st ¼ 0.27; 95% CI, 0.12-0.59, P trend ¼ 0.003) and positively associated with 2:16a-hydroxyestrone ratio (OR 4th quartile vs. 1st ¼ 2.44; 95% CI, 1.34-4.45, P trend ¼ 0.001). Individual 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. Cancer Epidemiol Biomarkers Prev; 23(11); 2374-82. Ó2014 AACR.

Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

“…There are various core regulatory factors and pathways in prostate cancer associated pathways ( hsa05215 ). Steroid hormone biosynthesis has been reported to contribute to the metastasis of prostate cancer and interacts with the specific oncogene of pancreatic cancer AR , implying its core role for the prostate associated pathways that we have predicted [51, 52]. According to recent publications, such core pathway of the steroid hormone biosynthesis may also contribute to pancreatic cancer, revealing the underlying relationships between prostate cancer associated pathways (as we have predicted, hsa05215) and pancreatic cancer [53, 54].…”

Sex Steroid Hormone Single-Nucleotide Polymorphisms, Pesticide Use, and the Risk of Prostate Cancer: A Nested Case–Control Study within the Agricultural Health Study

“…We identified hormone-related genes through a search of both the PubMed/Gene database and also the Kyoto Encyclopedia of Genes and Genomes (KEGG) catalog gene search tool using the terms “sex steroid hormone” or “hormone” or “testosterone” or “androgen” or “estrogen” in the keyword search. In addition, we sought information through a search of recent (last 5 years) topical literature reviews or original research studies evaluating the sex steroid hormone pathway to learn of common ways of identifying genes along this pathway (24–27). We excluded SNPs with a minor allele frequency less than 5% to allow for robust analysis of interactions between genetic loci and pesticide exposures.…”

Sex steroids in the tumor microenvironment and prostate cancer progression

“…Another study reported that serum E1, E2 and E1-S were commonly elevated in men with highgrade localized PCa (Giton et al 2008). Finally, others have reported the estrogen:androgen ratio is inversely related to the risk of aggressive PCa (Black et al 2014).…”