Urinary estrogen metabolites and prostate cancer: a case-control study and meta-analysis.
OBJECTIVE
To investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16alpha-hydroxyestrone (16alpha-OHE1) and 2-OHE1 to 16alpha-OHE1 ratio.


METHODS
We conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16alphaOHE1 and 2-OHE1 to 16alpha-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method.


RESULTS
We observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16alpha-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16alpha-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16alpha-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16alpha-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90).


CONCLUSIONS
Our study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study.
Barba
Maddalena
M
Department of Epidemiology, National Cancer Institute Regina Elena, Rome, Italy. maddalena.barba@gmail.com
Yang
Li
L
Schünemann
Holger J
HJ
Sperati
Francesca
F
Grioni
Sara
S
Stranges
Saverio
S
Westerlind
Kim C
KC
Blandino
Giovanni
G
Gallucci
Michele
M
Lauria
Rossella
R
Malorni
Luca
L
Muti
Paola
P
D000368:Aged; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D004967:Estrogens / Q000378:metabolism / Q000652:urine*; D006801:Humans; D006894:Hydroxyestrones / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000652:urine*; D012307:Risk Factors
D004967:Estrogens; D006894:Hydroxyestrones; C024980:2-hydroxyestrone