Format

Send to

Choose Destination
Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2374-82. doi: 10.1158/1055-9965.EPI-14-0700. Epub 2014 Sep 1.

Sex steroid hormone metabolism in relation to risk of aggressive prostate cancer.

Author information

1
Divisions of Cancer Epidemiology and Genetics and blacka@mail.nih.gov.
2
Cancer Prevention, National Cancer Institute, NIH, DHHS, Rockville, Maryland.
3
Washington University, St. Louis, Missouri.
4
Divisions of Cancer Epidemiology and Genetics and.
5
Cancer Prevention Institute of California, Fremont, CA and Stanford Cancer Institute, Palo Alto, California.
6
Surgeon General of the Army, Pharmacovigilance Center, U.S. Army Medical Command, Falls Church, Virginia.
7
C2N Diagnostics, Saint Louis, Missouri.
8
Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.

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 = 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 = 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 hormone-binding 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 (OR4th quartile vs. 1st = 0.27; 95% CI, 0.12-0.59, Ptrend = 0.003) and positively associated with 2:16α-hydroxyestrone ratio (OR4th quartile vs. 1st = 2.44; 95% CI, 1.34-4.45, Ptrend = 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.

PMID:
25178985
PMCID:
PMC4221438
DOI:
10.1158/1055-9965.EPI-14-0700
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center