Carcinogenesis Advance Access published online on November 4, 2004
Carcinogenesis, doi:10.1093/carcin/bgh326
© 2004 by Oxford University Press
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1 Population Studies and Prevention Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI
* To whom correspondence should be addressed. Glutathione S-transferases detoxify polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke by glutathione conjugation. Polymorphisms within the GSTM1, GSTT1 and GSTP1 genes, coding for enzymes with deficient or reduced activity, have been studied as potential modifiers of lung cancer risk. It is hypothesized that risk associated with potential susceptibility gene polymorphisms might be most evident at low levels of exposure. Never smokers developing lung cancer represent a highly susceptible subset of the population, exposed to tobacco carcinogens only through environmental tobacco smoke. This population-based case-control study examines the association between GSTM1, GSTT1 and GSTP1 genotypes and lung cancer in one of the largest samples of never smokers to date. Cases (n=166) were identified through the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and age- and race-matched population-based controls (n=181) were identified using random digit dialing. Overall, there was no significant association between single or combinations of genotypes at GSTM1, GSTT1 or GSTP1 and lung cancer risk after adjustment for age, race, sex, presence or absence of household environmental tobacco smoke (ETS) exposure, and household ETS exposure in years. However, in never smokers exposed to 20 or more years of household ETS, carrying the GSTM1 null genotype was associated with a 2.3-fold increase in risk (95% confidence interval (CI) 1.05-5.13). Individuals in this high ETS exposure category carrying the GSTM1 null and the GSTP1 Val allele were at over 4-fold increased risk of developing lung cancer (OR=4.56, 95% CI: 1.21-17.21). These findings suggest that in the presence of ETS, GSTM1 genotype both alone and in combination with GSTP1 genotype alter the risk of developing lung cancer among never smokers.
Revised September 30, 2004
Accepted October 26, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
GSTM1, GSTT1 and GSTP1 polymorphisms, environmental tobacco smoke exposure and risk of lung cancer among never smokers: a population-based study
2 Population Studies and Prevention Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI; Center for Molecular Medicine and Genetics, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI; Molecular Biology and Human Genetics Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI
A. S. Wenzlaff, E-mail: wenzlaff{at}med.wayne.edu
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