Susceptibility to lung cancer has been shown to be modulated by host specific factors. Inheritance of different polymorphic cytochrome P450s (CYPs) and the glutathione S-transferases (GSTs) which affect metabolism of environmental toxicants may play a key role in individual susceptibility. Although individual polymorphic genes have been reported to be associated with development of lung cancer, little is known about the combined effects of several genes in carcinogenesis. From our study of 54 lung cancer patients and 50 matched controls, we observed that a combination of several versions of 'unfavorable' metabolizing genes (CYP2D6, CYP2E1, GSTM1 and GSTT1) is strongly associated with lung cancer. The relative risk for the different combinations of these genotypes ranged between 1.3 and 14, with higher risk involving the activating genes. The duration and intensity of heavy smoking (expressed in pack-years) are the most important determinant for the development of lung cancer. For example, the estimated risk for development of lung cancer associated with smoking > 30 pack-years is represented by an odds ratio = 6.65 95% CL = 2.3-19.9 irrespective of an individual's genotype, whereas for smoking between > 30 and < 50 pack-years, odds ratio = 4.5; 95% CL = 1.37-15; and for smoking > 50 pack-years, odds ratio = 30; 95% CL = 5.7- 114. On the other hand, smoking of less than 30 pack-years is associated with an increased risk in the presence of the polymorphic genes (odds ratio = 2.5; 95% CL = 0.32-54). The results of our study indicate that the inheritance of multiple unfavorable genotypes, especially activating genes, is a crucial a predisposing factor for the development of lung cancer from cigarette smoking. In addition, the genes may cause moderate smokers who would normally outlive the deleterious effects of smoking to develop lung cancer. The information can therefore be used to target individuals for prevention of health problems.
|Number of pages||12|
|Journal||Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis|
|State||Published - Nov 28 1997|
Bibliographical noteFunding Information:
This study is supported by a grant to W.W.A. from the U.S. Environmental Protection Agency (R821003010) and by the NIH Center (P30 ES 06676)from the US National Institute of Health. The authors acknowledge the generous assistance from Dr. Randy Mifflin for his technical advice and Dr. Aravind B. Sankar for his help in recruiting the patients.
- Cigarette smoking
- Genetic polymorphism
- Lung cancer
- Molecular epidemiology
ASJC Scopus subject areas
- Molecular Biology
- Health, Toxicology and Mutagenesis