Lung cancer susceptibility: are we on our way to identifying a high-risk group?

Many studies have investigated lung cancer susceptibility based on the presence of low-penetrance, high-frequency single nucleotide polymorphisms. Identifying such susceptibility polymorphisms may lead to the development of tests that allow a more focused follow-up of a high-risk group. Genetic polymorphisms of xenobiotic metabolism, DNA repair, cell-cycle control, immunity, addiction and nutritional status have been described as promising candidates. Genetic polymorphisms in both metabolic activation (Phase I) and detoxification (Phase II) enzymes influence DNA damage. The DNA repair system is a critical cellular response that counteracts the carcinogenic effects of DNA. Thus, genetically determined susceptibility to carcinogens depends on the balance between metabolic and DNA repair enzymes. This review evaluates whether or not a specific polymorphism or a combination of such polymorphisms can effectively predict high-risk groups.