PMID: 9434875Jan 22, 1998Paper

Combined genetic polymorphism and risk for development of lung cancer

Mutation Research
R el-ZeinW W Au

Abstract

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,...Continue Reading

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