Carcinogenesis Advance Access published online on January 20, 2005
Carcinogenesis, doi:10.1093/carcin/bgi023
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1 Wayne State University School of Medicine, Detroit, Michigan
* To whom correspondence should be addressed. Polymorphisms in GSTM1, GSTT1 and GSTP1 genes in humans are associated with reduction of enzymatic activity towards several substrates, including those found in tobacco smoke. To investigate the potential role these polymorphisms have as modulators of early-onset lung cancer risk, a population-based case-control study involving early-onset lung cancer cases was performed. Biological samples were available for 350 individuals diagnosed prior to 50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 410 age, race and sex-matched controls ascertained through random digit dialing. African Americans carrying at least one G allele at the GSTP1 locus were 2.9-fold more likely to have lung cancer compared to African Americans without a G allele after adjustment for age, sex, pack years of smoking, and history of lung cancer in a first-degree relative (95% CI 1.29-6.20). African Americans with either one or two risk genotypes at the GSTM1 and GSTP1 loci were at increased risk of having lung cancer compared to those with fully functional GSTM1 and GSTP1 genes (OR=2.8, 95% CI 1.1-7.2 and OR=4.0, 95% CI 1.3-12.2, respectively). No significant single gene associations between GSTM1, GSTT1 or GSTP1 and early-onset lung cancer were identified in Caucasians, after adjusting for age, sex, pack years and family history of lung cancer. However, our results suggest that specific combinations of glutathione S-transferase polymorphisms increase risk of early-onset lung cancer. Joint analysis of these genotypes may identify individuals who are at higher risk of developing early-onset lung cancer with a greater certainty than single gene studies.
Received October 11, 2004
Revised December 22, 2004
Accepted January 8, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Combinations of glutathione S-transferase genotypes and risk of early-onset lung cancer in caucasians and African Americans: a population-based study
2 University of Michigan School of Public Health, Ann Arbor, Michigan
3 Molecular Biology and Human Genetics Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan
4 Wayne State University School of Medicine, Detroit, Michigan; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan
M. L. Cote, E-mail: cotem{at}med.wayne.edu
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