Journal of Experimental & Clinical Cancer Research Review BioMed Central Open Access Urinary estrogen metabolites and prostate cancer: a case-control study and meta-analysis Maddalena Barba1, Li Yang2, Holger J Schünemann1,3,4, Francesca Sperati1, Sara Grioni5, Saverio Stranges6, Kim C Westerlind7, Giovanni Blandino8, Michele Gallucci9, Rossella Lauria10, Luca Malorni10,11 and Paola Muti*12 Address: 1Department of Epidemiology, National Cancer Institute Regina Elena, Rome, Italy, 2Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska, USA, 3Department of Medicine, State University of New York at Buffalo, Buffalo, New York, USA, 4Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada, 5Nutritional Epidemiology Unit, National Cancer Institute, Milan, Italy, 6Health Sciences Research Institute, Warwick Medical School, Coventry, UK, 7Division of Endocrinology, Metabolism & Diabetes, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, USA, 8Translation Oncogenomics Unit/Lab B, National Cancer Institute Regina Elena, Rome, Italy, 9Department of Urology, National Cancer Institute Regina Elena, Rome, Italy, 10Division of Medical Oncology, Department of Molecular and Clinical Endocrinology and Oncology, University of Naples Federico II, Naples, Italy, 11Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas, USA and 12Scientific Direction, National Cancer Institute Regina Elena, Rome, Italy Email: Maddalena Barba - maddalena.barba@gmail.com; Li Yang - liyang@unmc.edu; Holger J Schünemann - hjs@buffalo.edu; Francesca Sperati - sperati@ifo.it; Sara Grioni - Sara.grioni@istitutotumori.mi.it; Saverio Stranges - S.Stranges@warwick.ac.uk; Kim C Westerlind - Kim.Westerlind@uchsc.edu; Giovanni Blandino - blandino@ifo.it; Michele Gallucci - gallucci@ifo.it; Rossella Lauria - rossellalauria@yahoo.it; Luca Malorni - malorni@bcm.edu; Paola Muti* - muti@buffalo.edu * Corresponding author Published: 8 October 2009 Journal of Experimental & Clinical Cancer Research 2009, 28:135 doi:10.1186/1756-9966-28-135 This article is available from: http://www.jeccr.com/content/28/1/135 Received: 22 July 2009 Accepted: 8 October 2009 © 2009 Barba et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Objective: To investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1) and 2-OHE1 to 16α-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, 16αOHE1 and 2-OHE1 to 16α-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 16α-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 16α-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 16α-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 16α-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90). Conclusion: Our study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study. Page 1 of 8 (page number not for citation purposes)