Lung Cancer: Molecular Markers of Occupational Carcinogens

Identification of exposure-specific molecular markers for occupationally derived lung cancer is influenced by several confounding factors, such as tobacco smoking and environmental exposures. Specific markers can be detected as gene products either in target tissues, such as lung or tumor tissue, or in surrogate tissues obtained with less invasive operations, such as blood, effusion fluid, sputum, bronchoalveolar lavage fluid, or in exhaled breath condensate. Asbestos-specific chromosomal and genetic alterations in lung cancer have been described in several chromosomes, e.g., 2p, 3p, 9, and 19p. Allelic imbalance or loss at 2p16, 9q33.1, and 19p13 has shown dose–response with asbestos exposure and can recognize asbestos-related lung cancer with high specificity. Several alterations, e.g., G to T transversion mutations of TP53, are likely caused by interaction of tobacco carcinogens and asbestos. Unique epigenetic miRNA and DNA methylome profiles have been associated with asbestos-related lung cancer. The development of clinically useful markers requires validations and the standardization of detection methods as well as an efficient combination of markers for molecular assays.