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American Journal of Epidemiology Advance Access originally published online on September 25, 2006
American Journal of Epidemiology 2006 164(11):1027-1042; doi:10.1093/aje/kwj321
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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.

Meta- and Pooled Analysis of GSTT1 and Lung Cancer: A HuGE-GSEC Review

S Raimondi1, V Paracchini1, H Autrup2, JM Barros-Dios3, S Benhamou4, P Boffetta5, ML Cote6, IA Dialyna7, V Dolzan8, R Filiberti9, S Garte10,11, A Hirvonen12, K Husgafvel-Pursiainen12, EN Imyanitov13, I Kalina14, D Kang15, C Kiyohara16, T Kohno17, P Kremers18, Q Lan19, S London20, AC Povey21, A Rannug22, E Reszka23, A Risch24, M Romkes11, J Schneider25, A Seow26, PG Shields27, RC Sobti28, M Sørensen29, M Spinola30, MR Spitz31, RC Strange32, I Stücker33, H Sugimura34, J To-Figueras35, S Tokudome36, P Yang37, J-M Yuan38, M Warholm22 and E Taioli11

1 Policlinico Milano, Milan, Italy
2 Institute of Public Health, University of Aarhus, Aarhus, Denmark
3 Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain
4 INSERM and Evry University, Evry, France
5 Genetics and Epidemiology Cluster, International Agency for Research on Cancer, Lyon, France
6 Karmanos Cancer Institute, Wayne State University, Detroit, MI
7 Department of Virology, University of Crete, Crete, Greece
8 Institute of Biochemistry, University of Ljubljana, Ljubljana, Slovenia
9 Department of Epidemiology and Biostatistics, National Cancer Research Institute, Genoa, Italy
10 Genetics Research Institute, Milan, Italy
11 Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA
12 Finnish Institute of Occupational Health, Helsinki, Finland
13 N. N. Petrov Institute of Oncology, St. Petersburg, Russia
14 Department of Medical Biology, School of Medicine, P. J. Safárik University, Kosice, Slovakia
15 Institute of Environmental Medicine, Seoul National University, Seoul, Korea
16 Department of Preventive Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
17 Biology Division, National Cancer Center Research Institute, Tokyo, Japan
18 Service of Medical Chemistry, Institute of Pathology, Sart Tilman Liège, Belgium
19 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
20 National Institute for Environmental Health Sciences, Research Triangle Park, NC
21 Centre for Occupational and Environmental Health, University of Manchester, Manchester, United Kingdom
22 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
23 Department of Toxicology and Carcinogenesis, Institute of Occupational Medicine, Lodz, Poland
24 Department of Toxicology and Cancer Risk Factors, DKFZ-German Cancer Research Center, Heidelberg, Germany
25 Institute of Occupational and Social Medicine, University of Giessen, Giessen, Germany
26 Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore
27 Cancer Genetics and Epidemiology, Georgetown University Medical Center, Washington, DC
28 Department of Biotechnology, Panjab University, Chandigarh, India
29 Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark
30 Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy
31 Department of Epidemiology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX
32 Centre for Cell and Molecular Medicine, Keele University, North Staffordshire Hospital, Staffordshire, England
33 INSERM Unit of Epidemiologic Statistic Research on the Environment and Health, Villejuif Cedex, France
34 First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan
35 Hospital Clinic Provincial Toxicology Unit, Barcelona, Spain
36 Department of Health Promotion and Preventive Medicine, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan
37 Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN
38 School of Public Health, University of Minnesota, Minneapolis, MN

Correspondence to Dr. Emanuela Taioli, University of Pittsburgh, Department of Epidemiology, 5150 Centre Avenue, Pittsburgh, PA 15232 (e-mail: taiolien{at}upmc.edu).

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10–20%) than among Asians (50–60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.

disease susceptibility; epidemiology; genes; genetic predisposition to disease; GSTT1; lung neoplasms; meta-analysis

Abbreviations: CI, confidence interval; GSEC, Genetic Susceptibility to Environmental Carcinogens; GST, glutathione S-transferase; GSTT1, glutathione S-transferase theta 1 gene; 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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