Genetic polymorphisms and lung cancer susceptibility: a review.

Department of Preventive Medicine, Division of Social Medicine, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka 812-8582, Japan. chikako@phealth.med.kyushu-u.ac.jp

Lung cancer is a major cause of cancer-related death in the developed countries and the overall survival rate has still an extremely poor. Cigarette smoking is an established risk factor for lung cancer although a possible role for genetic susceptibility in the development of lung cancer has been inferred from familial clustering of the disease and segregation analyzes. Everyone may have a unique combination of polymorphic traits that modify genetic susceptibility and response to drugs, chemicals and carcinogens. Developments in molecular biology have led to growing interest in investigation of biological markers, which may increase predisposition to lung carcinogenesis. Therefore, the high-risk genotype of an individual could be determined easily. As there are the great number of carcinogen-activating and -detoxifying enzymes, the variation in their expression and the complexity of exposures to tobacco carcinogens, the existence of multiple alleles at loci of those enzymes may result in differential susceptibilities of individuals. This review summarize data addressing the relationships of lung cancer to markers of genetic susceptibility genes, including metabolic polymorphisms other than well-investigated cytochrome P450s or glutathione S-transferases, DNA repair genes and the p53 tumor suppressor gene. Among genetic polymorphisms reviewed here, myeloperoxidase gene (a G to A mutation) and microsomal epoxide hydrolase exon 4 polymorphism (substitution of Arg for His) were significantly associated with lung cancer risk. As lung cancer is a multifactorial disease, an improved understanding of the interplay of environmental and genetic polymorphisms at multiple loci may help identify individuals who are at increased risk for lung cancer. Hopefully, in the future we will be able to screen for lung cancer susceptibility by using specific biomarkers. Copyright 2002 Elsevier Science Ireland Ltd.

PMID: 12234692 [PubMed - indexed for MEDLINE]