Lung Cancer OverviewEpidemiology of Lung Cancer Lung canceris the primary cause of cancer mortality in the United States and othercountries.1,2 Since 1985, lung cancer has been the most commoncancer worldwide in terms of incidence and mortality.1 In 2012,there were approximately 1.82 million new cases and 1.
59 million deaths of lungcancer worldwide.3,4 Therefore, the current burden of lung cancer ispossibly underestimated.1 Although in 1980 69% of lung cancer caseswere in developed countries, currently approximately 50% of cases occur indeveloping countries.1 According to Cheng and colleagues, lungcancer incidence was highest in very high HDI (Human Development Index)countries and lowest in low HDI countries.4 Furthermore, in mostcountries with high HDI, as male incidence continued to decrease, femaleincidence gradually increased.4 Since 1985, the global estimatednumber of lung cancer cases in men and women has increased by 51%.3 Relativesurvival rate ranges from 2% (Lybia) to 15.6% (United States) to 30% (Japan).
4Approximately 85% of the lung cancer cases are comprised of Non-small cell lungcancer (NSCLC).5 Today, immunotherapeutic strategies such asadoptive T-cell transfer, vaccines, and checkpoint inhibitors are undergoingdevelopments for the treatment of NSCLC.5 These latest techniquesare providing scientists with optimism for vastly improving lung cancertreatments. Etiologyof Lung Cancer Therelationship between tobacco smoking and lung cancer incidence has been provenin many ecological and clinical studies.3 Decline in lung cancerdeath rates in women started more than a decade after declining in men.1This lag is related to the fact that that cigarette smoking in women peaked twodecades later than in men.
1 Today, lung cancer incidence andmortality rate data indicate a promising change from the steep rise in the1970s and appear to be reaching a plateau.4 Generally, the incidence and mortalityrates are equal because most patients diagnosed with lung cancer die of it.1,4 In1964, the U.S. Public Health Service published a report in which they explainedthe negative effects of smoking on health, particularly, its progression oflung cancer.
6 Since the publication of this report, yearlyconsumption of cigarettes has declined in the United States.6 Moreover,prevalence of smoking is higher in adults below the federal poverty level and individualswith less than a high school diploma.6 Also, prevalence of smokingis higher in the South and Midwest regions of the United States.6 Thereare more than 4000 chemical constituents of cigarette smoke, and theInternational Agency for Research on Cancer (IARC) has identified at least 50carcinogens in tobacco smoke.7,8 The agents of concern in lungcancer are the tobacco-specific N-nitrosamines(TSNA), which are produced during tobacco processing and smoking.
7,8These carcinogens covalently bind to the DNA and form DNA adducts. If repairprocesses fail to remove these DNA adducts or the cells fail to undergoapoptosis, permanent mutations occur. Ultimately, these mutations lead touncontrolled cell division and tumor development.9 The lung cancer risk is proportionalto the quantity of cigarette consumption or degree of exposure to thecarcinogens.10 Other factors, such as individual susceptibility,also play a role in development of lung carcinoma.
1,2 Even thoughmore than 80% of lung cancers occur in people who had exposure to tobacco smokethroughout their lives, less than 20% of smokers (1 in 9) develop lung cancer.10Hence, it is important to consider environmental factors and geneticpredispositions when explaining variabilities in lung cancer susceptibility.1,10 Otherforms of smoking have been proven to contribute to lung cancer development.7Regular cigar and pipe smokers are at greater risk of developing lung cancer giventhat they are exposed to a larger quantity of carcinogens during their lifetimes.1Furthermore, histologic modifications similar to the premalignant stagehave been observed in the bronchial epithelium of regular marijuana and cocainesmokers.12,13 Ithas been reported that secondhand smoke contributes to approximately 17% oflung cancer in non-smokers who were exposed to high levels of environmentaltobacco smoke (ETS) in their childhood and adolescence.2,12Furthermore, wood smoke exposure and air pollution in industrialized nations havebeen attributed to lung cancer risk factor. Occupational carcinogens includingasbestos, radon gas, and diesel fumes among others have also been reported tohave a role in lung cancer development.
2,13 Approximately 15% of lung cancers inmen and 53% in women are not attributed to smoking.14 This accountsfor 25% of lung cancers worldwide.14 Moreover, the incidence of lungcancer in never-smokers appears to have a geographic variation across the globe.1Never-smoker women are more frequently affected than men.
Furthermore, smokersmainly develop SCLC and squamous cell carcinoma, but non-smokers are mostlyassociated with adenocarcinoma.15 Hereditarycomponents could also contribute to the lung cancer risk factors list.15,16Smoking history is associated with a 3-fold increase in the risk for peoplewith family history of lung cancer.16 A candidate susceptibilitygenes study has shown that there are genes of low penetrance and high frequencythat are associated with absorption, metabolism, and accumulation of tobacco andother carcinogens in the lung tissue.1 Host genetic factorsdetermine lung cancer susceptibility.
Therefore, persons with geneticpredispositions are at higher risk of developing lung cancer.16 Like many other cancers, lung cancer is also related to diet and obesity. Ithas been reported that low serum concentration of antioxidants could take partin development of lung cancer.17 On the other hand, there have beenstudies highlighting that lung cancer patients receiving Beta-Carotenesupplementation have a higher than expected mortality.18,19 Thesestudies, however unsettling, should serve to remind people that lack orexcessive intake of vitamins can potentially be harmful.1 Consumptionof raw fruit and vegetables has been reported to be associated with a decreasein the risk of lung cancer development. 20 In a study by Wu and colleagues,airway obstruction has been associated with lung cancer development.
21Additionally, certain infectious agents including human papillomavirus (HPV),Epstein-Barr virus, Chlamydia pneumonia, and pulmonary tuberculosis have been reported to be involved inthe development of lung cancer.1 A greater possibility ofcoinfection with oncogenic viruses has increased the risk of lung cancer in HIV-positiveindividuals.22 Basic Biology and Treatment Options Lungcancer appears in the cells of the lung and bronchus epithelium, which can bedivided to small cell lung cancer and non-small cell lung cancer.
1 Adenocarcinomais the most common type of lung cancer. The mechanism of damage of lung canceris very complex.5 Multiple levels of molecular alteration includinggenetics, epigenetics, and protein expression should be evaluated when it comesto prognostication, diagnosis, andtreatment of lung cancer.23 Identification of mutations such as ALKand EGFR have enabled scientist to develop targeted therapy for lungadenocarcinoma.23 Targeted therapy approach minimizes drug toxicity.5Nevertheless, only 20% of lung cancer cases have identifiable targets.
5,24Therefore, cytotoxic chemotherapy is the only treatment option for theremaining 80%.5,24 Today, enhancements in understanding themechanisms of immune system in response to cancer have led to development ofimmunotherapeutic methods for treatment of NSCLC.5 Activeimmunotherapeutic approach targets regulation of the host’s immune system. Incontrast, passive immunotherapeutic approach does not use the host’s immunemachinery.5 Monoclonal antibodies and adoptive T-cell transfer areexamples of passive immunotherapy strategies. DiseasePrevention and Proposed Solutions The first and mostrecommended approach to lung cancer prevention is abstaining from smoking andexposure to secondhand smoke. This is especially important for individuals whohave a family history of lung cancer. The U.
S. Preventive Service Task Force(USPSTF) and Center for Medicine and Medicaid Services have suggested annuallung cancer screenings for patients above 55 years who are or used to be heavysmokers.25 Furthermore, regardless of screening results, physicians andother healthcare professionals are urged to encourage patients to quit smoking duringevery visit.25 Smokers coming in for screening should be providedwith evidence-based, behavioral, and pharmacologic treatment options to aidthem in smoking cessation. 25 However, more research is needed todetermine the potential adverse effects of screening on smoking behavior.
6,25It is important to keep in mind that most of the patients that come in forscreening are lifetime smokers that started to smoke in their adolescence orearly adulthood. Therefore, a more comprehensive approach, such as educatingthe youth regarding the potential harms of smoking, could also help many peoplefrom being at a higher risk for developing lung cancer in the first place. Reference List 1.
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