The Main Types of Lung Cancer

Lung cancer is a disease of uncontrolled cell growth in tissues of the lung. This growth may lead to metastasis to adjacent tissues and infiltration beyond the lungs. The majority of primary lung cancers are derived from epithelial cells. Lung cancer is the most common cause of cancer-related death in men and women, and is responsible for 1.3 million deaths worldwide annually, as of 2004 (37).

The main types of lung cancer are small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). Depending on the type of lung cancer, the treatment varies: NSCLC is sometimes treated with surgery, while SCLC often responds better to chemotherapy and radiation (38). The most common cause of lung cancer is long-term exposure to tobacco smoke (39). The occurrence of lung cancer in nonsmokers, who account for as many as 15% of cases (40), is often attributed to a combination of genetic factors (41, 42) radon gas (43), asbestos (44) and air pollution (45-47) including secondhand smoke (48, 49). Undoubtedly, tobacco-smoke caused lung cancer is impacted by inter-individual genetic variability that in turn affects the metabolism of tobacco-smoke carcinogens, similar to genetic impact on the metabolism of therapeutic agents. In this case, however, variable metabolism results in variable levels of harmful DNA adducts, and ultimately to cancer-causing mutations, rather than to adverse effects, as is case from chemotherapeutic treatments.

The use of tobacco products continues to be an immense public health problem, and one might argue is the largest voluntary source of human exposure to carcinogens in the world. However, much progress has been made in the past 20 years, not only in understanding mechanisms of tobacco carcinogenesis, bu...

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...dering genetic variations within this gene are beginning to emerge, and are further emphasizing its importance (64-67).

Both, environmental and genetic factors play a role in a development of most diseases, and therefore it is important to understand the interactions between these factors. In all discussions of environmental exposure (environment being defined as any external agent, including medications), the dose to which an individual is exposed is critical. Therefore, it is crucial to understand gene—environment interaction. The idea of genetic variants modifying risk for cancer upon exposure to varying levels of external agents first came from studies of metabolic genes in environmental carcinogenesis (68, 69). A portion of this thesis investigates gene—environment relationship in lung cancer by studying variations in the known environmental exposure pathways.