pulmonary disorders
Lung Carcinoma
Etiology of Lung Carcinoma
Themost important cause of lung cancer,accounting for about 85% of cases, is Cigarette smoking ( Etiology references ) The risk of cancer differs by age, smoking intensity, and smoking duration. The risk of lung cancer increases with combined exposure to toxins and cigarette smoking. Other confirmed or possible risk factors include air pollution, marijuana smoking, exposure to cigar smoke and second-hand cigarette smoke, and exposure to carcinogens (eg, asbestos, radiation, radon, arsenic, chromates, nickel, chloromethyl ethers, polycyclic aromatic hydrocarbons, mustard gas, coke-oven emissions, smoke from primitive cooking or heating fires in huts). The lung cancer risk associated with electronicnicotinedelivery systems (eg, e-cigarettes) remains to be determined, although it is thought that the products of combustion of tobacco are the primary carcinogens. The risk of cancer declines after smoking cessation, but it never returns to the baseline risk in people who have never smoked. About 15 to 20% of people who develop lung cancer have never smoked or have smoked minimally. Exposure to household radon increases lung cancer risk and is the second leading cause of lung cancer in the United States ( Etiology references ). Chronic inflammation increases the risk of many cancers, including lung cancer. For example, Chronic Obstructive Pulmonary Disease (COPD) (chronic obstructive pulmonary disease), Respiratory epithelial cells require prolonged exposure to cancer-promoting agents and accumulation of multiple genetic mutations before becoming neoplastic (an effect called field carcinogenesis). In some patients with lung cancer, secondary or additional mutations in genes that stimulate cell growth (KRAS,MYC) or cause abnormalities in growth factor receptor signaling (EGFR, HER2)can contribute to the uncontrolled proliferation of abnormal cells. In addition, mutations that inhibit tumor-suppressor genes (eg,TP53,APC) can lead to cancer. Other mutations that may be responsible include theEML4-ALKtranslocation and mutations inROS1,BRAF, andPIK3CA. mutations [ Etiology references ]). The second LCMC study accrued 904 patients with stage IV lung cancer who had at least one 14 cancer-related gene tested for and found that oncogenic driver mutations were present in more than half of the patients with adenocarcinoma and that targeted therapies improved survival ( 1.Division of Cancer Prevention and Control, Centers for Disease Control and Prevention: What Are the Risk Factors for Lung Cancer? Reviewed October 25, 2022. Accessed April 24, 2023 2.U.S. Cancer Statistics Working Group: U.S. Cancer Statistics Data Visualizations Tool, based on 2021 submission data (1999-2019): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; https://www.cdc.gov/cancer/dataviz, released in November 2022 3.Kris MG, Johnson BE, Berry LD, et al: Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs.JAMA311 (19):1998–2006, 2014. doi: 10.1001/jama.2014.3741 4.Aisner DL, Sholl LM, Berry LD, et al: The Impact of Smoking and TP53 Mutations in Lung Adenocarcinoma Patients with Targetable Mutations-The Lung Cancer Mutation Consortium (LCMC2).Clin Cancer Res24(5):1038-1047, 2018. doi:10.1158/1078-0432.CCR-17-2289 