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American Journal of Epidemiology Advance Access originally published online on February 24, 2009
American Journal of Epidemiology 2009 169(7):802-814; doi:10.1093/aje/kwn417
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American Journal of Epidemiology © The Author 2009. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Meta- and Pooled Analysis of GSTP1 Polymorphism and Lung Cancer: A HuGE-GSEC Review

Michele L. Cote, Wei Chen, Daryn W. Smith, Simone Benhamou, Christine Bouchardy, Dorota Butkiewicz, Kwun M. Fong, Manuel Gené, Ari Hirvonen, Chikako Kiyohara, Jill E. Larsen, Pinpin Lin, Ole Raaschou-Nielsen, Andrew C. Povey, Edyta Reszka, Angela Risch, Joachim Schneider, Ann G. Schwartz, Mette Sorensen, Jordi To-Figueras, Shinkan Tokudome, Yuepu Pu, Ping Yang, Angela S. Wenzlaff, Harriet Wikman and Emanuela Taioli

Correspondence to Dr. Michele L. Cote, Population Studies and Prevention, Karmanos Cancer Institute, Internal Medicine, Wayne State University School of Medicine, 110 East Warren, Detroit, MI 48201 (e-mail: cotem{at}med.wayne.edu).

Received for publication June 11, 2008. Accepted for publication December 18, 2008.

Lung cancer is the most common cancer worldwide. Polymorphisms in genes associated with carcinogen metabolism may modulate risk of disease. Glutathione S-transferase pi (GSTP1) detoxifies polycyclic aromatic hydrocarbons found in cigarette smoke and is the most highly expressed glutathione S-transferase in lung tissue. A polymorphism in the GSTP1 gene, an A-to-G transition in exon 5 (Ile105Val, 313A -> 313G), results in lower activity among individuals who carry the valine allele. The authors present a meta- and a pooled analysis of case-control studies that examined the association between this polymorphism in GSTP1 and lung cancer risk (27 studies, 8,322 cases and 8,844 controls and 15 studies, 4,282 cases and 5,032 controls, respectively). Overall, the meta-analysis found no significant association between lung cancer risk and the GSTP1 exon 5 polymorphism. In the pooled analysis, there was an overall association (odds ratio = 1.11, 95% confidence interval: 1.03, 1.21) between lung cancer and carriage of the GSTP1 Val/Val or Ile/Val genotype compared with those carrying the Ile/Ile genotype. Increased risk varied by histologic type in Asians. There appears to be evidence for interaction between amount of smoking, the GSTP1 exon 5 polymorphism, and risk of lung cancer in whites.

Asian continental ancestry group; epidemiology; glutathione S-transferase pi; GSTP1; lung neoplasms; smoking

Abbreviations: CI, confidence interval; GSEC, Genetic Susceptibility to Environmental Carcinogens; GSTP1, glutathione S-transferase pi; OR, odds ratio; PAH, polycyclic aromatic hydrocarbon

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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