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American Journal of Epidemiology Advance Access originally published online on April 2, 2007
American Journal of Epidemiology 2007 165(11):1221-1230; doi:10.1093/aje/kwm003
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American Journal of Epidemiology Copyright © 2007 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Pooled Analysis and Meta-analysis of the Glutathione S-Transferase P1 Ile 105Val Polymorphism and Bladder Cancer: A HuGE-GSEC Review

Eliane Kellen1, Marjolein Hemelt2, Karin Broberg3, Klaus Golka4, Vessela Nedelcheva Kristensen5, Rayjean J. Hung6, Giuseppe Matullo7, Rama D. Mittal8, Stefano Porru9, Andrew Povey10, Wolfgang A. Schulz11, Jianhua Shen12, Frank Buntinx1,13, Maurice P. Zeegers1,2 and Emanuela Taioli14

1 Department of General Practice, Katholieke Universiteit Leuven, Comprehensive Cancer Institute Limburg, Limburg, Belgium
2 Unit of Genetic Epidemiology, Department of Public Health and Epidemiology, University of Birmingham, Birmingham, United Kingdom
3 Department of Occupational and Environmental Medicine and Psychiatric Epidemiology, Lund University, Lund, Sweden
4 Institute for Occupational Physiology at the University of Dortmund, Dortmund, Germany
5 Department of Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo, Norway
6 Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
7 Department of Genetics, Biology and Biochemistry, Faculty of Medicine and Surgery, University of Torino and ISI Foundation, Torino, Italy
8 Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh, India
9 Institute of Occupational Health, University of Brescia, Brescia, Italy
10 Centre for Occupational and Environmental Health, Medical School, University of Manchester, Manchester, United Kingdom
11 Department of Urology, Heinrich Heine University, Duesseldorf, Germany
12 Laboratory of Toxicology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
13 Department of General Practice and Research Institute Caphri, Maastricht University, Maastricht, the Netherlands
14 University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA

Correspondence to Eliane Kellen, Academisch Centrum voor Huisartsgeneeskunde, Kapucijnenvoer 33, Blok J, 3000 Leuven, Belgium (e-mail: Eliane.Kellen{at}med.kuleuven.be).

Received for publication August 14, 2006. Accepted for publication November 17, 2006.

The glutathione S-transferase P1 genotype (GSTP1) is involved in the inactivation of cigarette smoke carcinogens, and sequence variation in the gene may alter bladder cancer susceptibility. To examine the association between GSTP1Ile 105Val and bladder cancer, the authors undertook a meta- and pooled analysis. Summary crude and adjusted odds ratios and corresponding 95% confidence intervals were pooled by using a random-effects model. In the meta-analysis (16 studies, 4,273 cases and 5,081 controls), the unadjusted summary odds ratios for GSTP1 Ile/Val and Val/Val compared with GSTP1 Ile/Ile were 1.54 (95% confidence interval: 1.21, 1.99; p < 0.001) and 2.17 (95% confidence interval: 1.27, 3.71; p = 0.005). The association appeared to be the strongest in Asian countries. When the analysis was limited to European descendents (nine studies), the summary odds ratio decreased (odds ratio = 1.24, 95% confidence interval: 1.00, 1.52) (Q = 17.50; p = 0.02). All relevant data previously contributed to the International Study on Genetic Susceptibility to Environmental Carcinogens were pooled (eight studies, 1,305 cases and 1,558 controls). The summary odds ratios were similar to the ones from the meta-analysis. Case-only analyses did not detect an interaction between the GSTP1 genotype and smoking status (never/ever). GSTP1 Ile 105Val appears to be associated with a modest increase in the risk of bladder cancer.

epidemiology; GSTP1; meta-analysis; urinary bladder neoplasms

Abbreviations: CI, confidence interval; GSEC, Genetic Susceptibility to Environmental Carcinogens; GSTP1, glutathione S-transferase P1 genotype; OR, odds ratio

Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).


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