Risk Factors for Lung Cancer in Never Smokers: A Recent Review Including Genetics

摘要

Lung cancer, a disease traditionally attributed to the effects of carcinogens from inhaled tobacco smoke, is now recognised in a population with either a relatively light history of smoking, or never smoking. Although second hand smoke contributes to the risk of neoplasia, the extent to which this affects different individuals varies, and probably depends on a combination of genetic, environmental, and racial factors. In addition, there are known associations of lung cancer in never-smokers with different occupational factors, such as asbestos, as well as potential risks due to naturally occurring diseases, and lifestyle factors. In recent years, targeted molecular therapies of non-small-cell lung cancer have enabled prolonged disease-free-survival times. These are based on the detection of activating mutations or translocations of genes coding for receptor tyrosine kinases, such as EGFR and ALK. They are reported usually in adenocarcinomas, and are often diagnosed in never smoking individuals or light smokers. This has supported the evolving concept of lung cancer in never-smokers as a molecularly different subtype, with its own associated clinical characteristics and histopathological features. Furthermore, genome-wide association studies have suggested that there are genetic polymorphisms, conferring an increased risk of lung cancer, which have a greater impact on the risk in never-smokers compared to smokers.This review considers the different factors that may lead to lung cancer in those considered never-smokers and, where possible, examines these in the context of relevant genetic findings.