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American Journal of Epidemiology Advance Access published online on October 19, 2006
American Journal of Epidemiology, doi:10.1093/aje/kwj365
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.
Received April 14, 2006
Accepted May 26, 2006

HUMAN GENOME EPIDEMIOLOGY (HuGE) REVIEW

Meta- and Pooled Analyses of the Cytochrome P-450 1B1 Val432Leu Polymorphism and Breast Cancer: A HuGE-GSEC Review

Valentina Paracchini 1, Sara Raimondi 1, Inger T. Gram 2, Daehee Kang 3, Neslihan A. Kocabas 4, Vessela N. Kristensen 5, Donghui Li 6, Fritz F. Parl 7, Tove Rylander-Rudqvist 8, Pavel Soucek 9, Wei Zheng 10, Sara Wedren 11, and Emanuela Taioli 12 *

1 Scientific Direction, Ospedale Maggiore, Milan, Italy
2 Department of Preventive Medicine, Faculty of Medicine, Institute of Community Medicine, University of Tromsø, Tromsø, Norway
3 Department of Preventive Medicine, Seoul National University, College of Medicine, Institute of Environmental Medicine, Seoul, South Korea
4 Department of Toxicology, Faculty of Pharmacy, Gazi University, Ankara, Turkey
5 Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo, Norway
6 Department of Gastrointestinal Medical Oncology, M. D. Anderson Cancer Center, University of Texas, Houston, TX
7 Department of Pathology, Vanderbilt University Medical Center, Nashville, TN
8 Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
9 Center of Occupational Diseases, National Institute of Public Health, Prague, Czech Republic
10 Center for Health Services Research, Vanderbilt University Medical Center, Nashville, TN
11 Department of Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
12 University of Pittsburgh Cancer Institute, Pittsburgh, PA

* To whom correspondence should be addressed.
Emanuela Taioli, E-mail: taiolien{at}upmc.edu


  Abstract

The association between the cytochrome P-450 1B1 (CYP1B1) Val432Leu polymorphism and breast cancer was assessed through a meta-analysis of all published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database (http://www.upci.upmc.edu/research/ccps/ccontrol/g_intro.html). GSEC is a collaborative project that gathers information on studies of metabolic gene polymorphisms and cancer. Thirteen articles were included in the meta-analysis (14,331 subjects; 7,514 cases, 6,817 controls); nine data sets were included in the pooled analysis (6,842 subjects; 3,391 cases, 3,451 controls). A summary meta- or pooled estimate of the association between the CYP1B1 Val432Leu polymorphism and breast cancer could not be calculated because of statistically significant heterogeneity in the point estimates among studies. No association between the CYP1B1 Val432Leu polymorphism and breast cancer was observed in Asians (for Val/Val and Val/Leu combined, odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.8, 1.2). An inverse association was observed in populations of mixed/African origin (OR = 0.8, 95% CI: 0.7, 0.9). The pooled analysis suggested a possible association in Caucasians (for Val/Val and Val/Leu combined, OR = 1.5, 95% CI: 1.1, 2.1), with effect modification across age categories. The observed effect of age on the association in Caucasians indicates that further studies are needed on the role of CYP1B1 Val432Leu in estrogen metabolism according to age, ethnicity, and menopausal status.

Keywords: breast neoplasms; CYP1B1; cytochrome P-450 enzyme system; genetics; hormones; meta-analysis; polymorphism, genetic; review [publication type].
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