Lung Cancer Causes and Consequences

Lung Cancer Causes and Consequences James D. Crapo, MD University of Colorado Denver Denver, CO crapoj@njc.org

James D. Crapo, M.D., is a professor of medicine at the University of Colorado Denver, Division of Pulmonary Sciences and Critical Care. He is also chair of the Department of Medicine at the National Jewish Center. Dr. Crapo has numerous publications, including in the area of pulmonology. He specializes in internal medicine and pulmonary disease.

Lung Cancer Causes and Consequences Table of Contents I. Smoking and Lung Cancer...529 II. Asbestosis...529 III. Asbestosis and Lung Cancer...529 IV. Interstitial Lung Disease and Lung Cancer...530 V. Lung Distribution of Lung Cancer Compared to Deposition of Smoke and Asbestos Fibers...530 VI. Inflammation Mechanism Linking Asbestosis and Lung Cancer...530 VII. References...531 Lung Cancer Causes and Consequences Crapo 527

Lung Cancer Causes and Consequences I. Smoking and Lung Cancer Cancer Prevention Study I (CPS-I) (study period 1959-1965) by American Cancer Society. Relative risk = 11.35 for men and 2.69 for women. Cancer Prevention Study II (CPS-II)- (study period 1982-1988) by American Cancer Society. Relative risk = 22.36 for men and 11.94 for women. Thun, et al (2013) (study period 2000-2010). Relative risk = 24.97 for men and 25.66 for women. Daily cigarette consumption peaked in the 1960s for men and during the 1980s for women. Typical age at initiation of smoking is 15-19 years old for men and for women. Mean duration of smoking is 35-50 years. Development of COPD in a smoker is associated with a 2-4 fold increase in risk of lung cancer. Life Expectancy: Shortened by >10 years among current adult smokers compared with never smokers. Quiting smoking at age 25-34 results in a gain in life expectancy of about 10 years. Quiting smoking at age 35-44 results in a gain in life expectancy of about 9 years. Quiting smoking at age 45-54 results in a gain in life expectancy of about 6 years. II. Asbestosis Radiographic evidence of asbestosis (0/1, and greater) has been associated with increased risk of lung cancer with the magnitude of risk directly associated with severity of the asbestosis. All major types of lung cancer have been shown to occur at increased frequency in smokers when asbestosis is present (eg: squamous cell, adenocarcinoma, large cell and small cell). Threshold of exposure below which no cases of asbestos are expected to occur is 25 f/cc/years. Incidence of asbestosis at 75 to 100 f/cc/years of exposure is 1-2%. New cases of asbestosis are now rare due to Industrial Hygiene controls that were established in 1970s-1980s. Asbestosis usually occurs/initiates in proximity in time to when high level exposures occurred. Pulmonary fibrosis beginning decades after asbestos exposure is more likely due to another cause, such as IPF. III. Asbestosis and Lung Cancer Synergism between asbestos exposure and lung cancer is actually a synergism with asbestosis. Cohorts with no asbestosis have no increased risk of lung cancer. Cohorts with only low level asbestos exposure have no increased risk of lung cancer. Within cohorts with asbestosis, when studied, only subjects with asbestosis show an increased association with lung cancer. Lung Cancer Causes and Consequences Crapo 529

Pleural plaques are a marker of asbestos exposures, but not a reliable marker of increased risk for lung cancer. Animal inhalation studies show excess lung tumors only when lung fibrosis is produced. IV. Interstitial Lung Disease and Lung Cancer Lung fibrosis of many different etiologies has been associated with an increased risk of lung cancer (Meyer, et al 1965, Fraire & Greenberg 1973, Turner-Warwick, et al 1980). V. Lung Distribution of Lung Cancer Compared to Deposition of Smoke and Asbestos Fibers The majority of lung cancers occur in the proximal airways, commonly at airway bifurcations. Asbestos fibers are retained in the distal lung parenchyma, with fibers rarely found in the walls of the more proximal airway walls. The distribution of tobacco smoke residue accumulation correlates with the common distribution of lung cancers. VI. Inflammation Mechanism Linking Asbestosis and Lung Cancer Rom, Travis & Brody (1991) Asbestosis is an inflammatory and fibrotic process... mediated, at least in part, by cytokines released by alveolar macrophages... The processes of inflammation, fibrosis, and carcinogenesis appear to be closely inter-twined. For example, proto-oncogenes such as c-sis (PDFG-B-chain) are upregulated in activated alveolar macrophages from fibrotic lungs; these and possibly others may play an important role in asbestos carcinogensis. 530 Asbestos Medicine November 2013

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