Cigarettes and Lungs Cancer - Research Paper Example

 RUNNING HEAD: Cigarette Smoking and Lung Cancer Cigarette Smoking and Lung Cancer Introduction Cigarette smoking leads to several health issues one of which is lung cancer (Schroeder, 2013). Smoking not only increases the risk of lung cancer, but also interferes with treatment of lung cancer. Though there are several etiological factors incriminated in the development of lung cancer, smoking has proven to be the single most consistent link towards development of lung cancer. Cigarette smoking yields several substances including nicotine which have the potential to trigger oncogenes or suppress tumor suppressor genes and predispose to the development of lung cancer (Molina et al, 2008). Since lung cancer is associated with high morbidity and mortality and is the leading cause of cancer-related mortality worldwide, public, health providers and government policies are currently aimed at educating people to avoid smoking. In this article, cigarette smoking in the perspective of lung cancer, will be discussed along with strategies for prevention. Cigarette smoking and lung cancer Lung cancer is one of the leading causes of cancer-related mortality all over the world. Despite that, its incidence is actually decreasing (Molina et al, 2008). There are basically 2 predominant types of lung cancer and they are small cell lung cancer or SCLC and non-small cell lung cancer or NSCLC. The latter constitutes 85% of all lung cancer cases. NSCLC is further divided into large cell carcinoma, squamous cell carcinoma and adenocarcinoma (Molina et al, 2008). All these types of lung cancers are different in terms of clinical presentation and histopathological characteristics. But management plans and prognoses are similar. The most frequently encountered NSCLC is adenocarcinoma arising from the mucosal glands of the bronchi. It represents 35-40 percent of all lung cancers. It is mostly seen in the peripheral portion of the lung. It is the most common histologic subtype. It can also manifest as scar cancer. This subtype is mostly seen in non-smokers and may present as bronchoalveolar form of multifocal tumors. Squamous cell carcinoma accounts for about 25 percent of lung cancers. Unlike adenocarcinoma, the cancers are mainly seen in the central parts of the lungs with classical clinical presentation being proximal bronchus cavity. It is characterized by keratin pearls and has the tendency to exfoliate. It is often associated with hypercalemia. 10-15 percent of lung cancers are caused due to large cell carcinoma that is easily diagnosable by chest X-ray. Lung cancer metastatises to liver, bones, adrenal glands, brain, spinal cord and pericardium (Molina et al, 2008). Regional incidence pertaining to lung cancer is actually variable and it predominantly depends on the prevalence of cigarette smoking. For instance, in Utah, the incidence of lung cancer is lowest and smoking is lowest there (Molina et al, 2008). On the other hand, in Kentucky, the incidence of smoking is highest and so is the case with lung cancer (Molina et al, 2008). Another interesting aspect is, with the decline in the prevalence of smoking, the incidence of lung cancer is predominant in former smokers than in current smokers. For example, according to a study by Yang et al (2005), "more than 5000 patients whose lung cancer was diagnosed between 1997 and 2002, only 25% were current smokers and more than 60% were former smokers" (cited in Molina et al, 2008). The epidemic of lung cancer in the 20th century is undoubtedly caused by cigarette smoking. The development of lung cancer secondary to smoking is directly related to the number of cigarettes smoked per day and the duration of smoking. The nicotine content and tar content also influence the development of lung cancer. Tobacco contains about 300 substances that are harmful of which more than 60 are potent carcinogens (Lee, 2001). Nitrosamine-NNK and poly-aromatic hydrocarbons for DNA adducts leading to DNA damage. Benzo-A-pyrine causes induction of AKT molecular signaling, induction of mutation in tumor suppressor genes like p53. Cigarette smoke contains more than 60 known carcinogens like benzopyrene, nitrosamine and radon decay sequence (Lee, 2001). In addition to these, nicotine depresses immune responses against development of cancer. It is proven that 80-90 percent of lung cancer cases are due to smoking alone. One of the important carcinogenic agent in cigarette smoking is nicotine. Nicotine is one of the products of tobacco. The component undergoes several pathways of metabolism. During the process of smoking and curing, nicotine gets converted to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, and N’- nitrosonornicotine by means of nitrosation. After entering the body, the ingredient is rapidly absorbed and distributed widely in the body. 75% of nicotine is metabolized to cotinine by aldehyde oxidase, P450 (CYP) 2A6 and CYP2B6. Additional hydroxylation converts it to 3-OH cotinine which undergoes glucuronidation and excretion in urine. The remaining nicotine is converted to nicotine-N-oxide and other metabolites which are also excreted in urine. The role of nicotine is tumor promoter and not tumor initiator. Nicotine has tumor promoting activities. Nicotine, along with its metabolites can promote growth of tumor by means of angiogenesis, increased proliferation, invasion, migration, transition of cells from epithelial cells to mesenchymal cells and stimulation of autocrine loops with growth of tumor. Other than tumor stimulation and growth, nicotine can also lead to decreased effectiveness of cancer treatments like radiotherapy and chemotherapy. Nicotine activates the nicotinic acetylcholine receptors and also the beta-adrenergic receptors causing activation of signal transduction pathways which cause tumor progression and indulge in development of tumor resistance. Thus, it is clear that nicotine from cigarette smoke or other tobacco-related products causes promotion of development and progression of cancer and resistance to treatment related to cancer (Warren and Singh, 2013). Passive smoking also has been incriminated in the pathogenesis of lung cancer. Certain studies have shown that passive smoking can be more dangerous than cigarette smoking. Highest rates of passive smoking exposure is seen in cafes, restaurants and bars, followed by work place and then homes of relatives, friends and acquaintances. The quality and lifespan of smokers depends on the severity and number of smoking related illness and other associated comorbid conditions. Consumption of alcohol and other illicit drugs, sedentary lifestyle and stresses life can increase the mortality and mobility related to smoking (Bernstein, 2006). The development of lung cancer is initiated by activation of certain oncogenes or inactivation of tumor suppressor genes. Exposure to carcinogens like cigarette smoking causes conversion of protooncogenes to oncogenes which make individuals susceptible to develop cancer. Mutation and thereafter amplification of EGFR lead to NSCLC. Another gene which is less frequently affected is the Her2/neu gene. Damage to the chromosomes can lead to loss of heterozygosity and this can lead to inactivation of tumor suppressor genes. In SCLC, damage to 5q, 3p, 13g and 17p are common. In 60-75 percent of the cases, the p53 tumor suppressor gene that is located on the 17p chromosome is affected. Other genes which have been involved are BRAF, LKB1, PIK3CA, c-MET and NKX2-1 (Herbst et al, 2008). Currently, multiple hit theory causes toxic cellular insults that disrupts genetic reproduction. Genetic susceptibility is one of the important features in the development of cancer. The most common genetic abnormalities have been linked to ras family of oncogenes. These include K-ras, H-ras and N-ras. The genes encode a protein on the cell membrane’s inner surface with GTPase activity and this gets involved in signal transduction. Several studies performed on rats have suggested the involvement of ras mutations in the pathogenesis of NSCLC. These mutations are specifically noted in cancers that have developed secondary to smoking. Infact, K-ras factor is an independent prognostic factor. There are various studies that are being performed to develop management plans based on absence or presence of mutations of ras genes (Molina et al, 2008). Since most adult smokers begin smoking at young age, it is every important to ascertain and understand the causes of smoking in young children so that predictors of smoking can be evaluated and targeted for prevention. Several risk factors have been studied in this regard. According to the Liverpool Longitudinal Smoking Study (Smith et al, 2009), deprivation at both school and home was strongly associated with smoking among adolescents. The trial of smoking is influenced by several school-related environmental factors like peer groups. Smoking trial at the age of thirteen is most associated with the amount of time spent in smoky places. It is also predicted by the smoking rules of their respective house hold. From 14-16 years of age, both school deprivation and household smoking rules predicted smoking trial. The WHO (2003; cited in IRC, 2009) orders that: "Healthcare providers should not miss any opportunity to advocate and advise treatment strategies to people wishing to quit. The role of policy-makers, professionals and researchers will also be imperative in putting smoking cessation on the agenda.” According to the International Union Against Cancer (IRC, 2009), "health-care professionals have a duty to provide counseling and treat tobacco dependence as they would any other disease or addiction." The New Zealand National Advisory Committee on Health and Disability (2002; cited in IRC, 2009) states that “there is good evidence that even brief advice from health professionals has a significant effect on smoking cessation rates.” The World Health Organization Framework Convention on Tobacco Control or FCTC is a treaty ratified and signed by 145 countries all over the world. According to the treaty, "all governments must incorporate the diagnosis and treatment of tobacco dependence and counseling services on cessation of tobacco use in national health and educational programmes." The FCTC states that "given the diversity of countries’ economic situations, regulatory regimes and health care systems, the effort to treat tobacco dependence requires a multi-faceted approach. Therefore, a tobacco control program should not only encourage tobacco users to quit but also provide assistance in doing so." The services which have been recommended to be introduced are health education in the form of tobacco product packaging, counseling services like intensive behavioral support by appropriate specialists, and maternal and child health clinics. The FCTC also recommends to "level the regulatory playing field” between tobacco and pharmaceutical products, "provide protection from secondhand smoke" and "present cessation-oriented messages on all cigarette packages." The WHO promotes cessation of smoking through 3 strategies: the public health approach, the health systems approach and the surveillance, research and information approach (WHO, 2009). Key areas in which research is going on for cessation of smoking is evaluation of various policies and interventions for tobacco control, influences of environments on smoking and also smoking-related behaviors, relationship between use of tobacco and health inequalities, impact of passive smoking on health and modes of controlling passive smoke, regulation and behavior or tobacco and tobacco-related products industry and finally investigation of formation and implementation of various tobacco control policies (Signal et al, 2001). Conclusion Smoking, both active and passive, undoubtedly, is one of the important causative factors of lung cancer. Tobacco has several carcinogenic substances which cause lung cancer by stimulating oncogenes and by suppressing tumor suppressor genes. Nicotine, the addictive substance in tobacco, along with its metabolites can promote growth of tumor by means of angiogenesis, increased proliferation, invasion, migration, transition of cells from epithelial cells to mesenchymal cells and stimulation of autocrine loops with growth of tumor. The development of lung cancer in an individual is dependent on the number of pack years, the type of cigarette used and also individual susceptibility to development of cancer due to genetic predisposition. Smoking also interferes with lung cancer treatment and hence stopping of smoking is crucial for the management of lung cancer. It is very important to educate people about the hazards of smoking risk from childhood and this must include about passive smoking too. Various government policies must be introduced to strictly curb the smoking mania, especially among adolescents. References Bernstein, S.L. (2006). Cigarette smoking. EmedicineHealth. Retrieved on 26th April, 2013 from http://www.emedicinehealth.com/cigarette_smoking/page12_em.htm#Authors%20and%20Editors Cataldo, J.K., Dubey, S., Prochaska, J.J. (2010). Smoking Cessation: An Integral Part of Lung Cancer Treatment. Oncology, 78(5-6), 289-301. International Resource Center or IRC. (2009). Fact Sheet: Tobacco Cessation and Treatment. Retrieved on 26th April, 2013 from http://www.tobaccofreecenter.org/tobacco_cessation_treatment Lee PN. (2001). Lung cancer and type of cigarette smoked. Inhal Toxicol., 13(11), 951-76. Molina, J.R., Yang, P., Cassivi, S.D., Schild, S.E., Adjei, A.A. (2008). Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc.,83, 584-594. Herbst, R.S. Heymach, J.V., Lippman, S.M. (2008). Lung cancer. New England Journal of Medicine, 359 (13), 1367–1380. Smith, D., Smith, H., Woods, S., and Springett, J. (2009). Smoking environments and adolescent smoking: evidence from the Liverpool Longitudinal Smoking Study. JEHR, 9(1). Retrieved on 26th April, 2013 from http://www.cieh.org/jehr/adolescent_smoking_liverpool.aspx Schroeder, S.A. (2013). New evidence that cigarette smoking remains the most important health hazard. N Engl J Med., 368(4), 389-90. WHO (2009). Policy recommendations for smoking cessation and treatment of tobacco dependence. Retrieved on 13th March, 2011 from http://www.who.int/tobacco/resources/publications/tobacco_dependence/en/index.html Warren, G.W., Singh, A.K. (2013). Nicotine and lung cancer. J Carcinog., 31;12:1 Read More