Connection Between Smoking and Lower-Income Households

4516 words (18 pages) Essay

23rd Sep 2019 Health Reference this

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Lung Cancer, p53 mutation with SV40, and the Connection Between Smoking and Lower-Income Households

According to Gibbons, Byers, and Kurie (2014), “Tobacco exposure is the leading cause of cancers involving the oral cavity, conductive airways, and the lung” (p. 3). Under the same article, the challenge to highlight the health risks of tobacco exposure has been an active topic for more than 50 years in the United States. Tobacco consists many carcinogens that carry several complications of genomic mutations such as the tumor suppressor gene, p53. With the presence of a mutation on gene p53, its vital cellular functions are performed adequately creating high chances of developing cancers early in one’s lifetime. This capstone paper will include the linking lung cancer and genetic mutations with the human lungs after the exposure of tobacco, cellular roles of p53 under typical and altered conditions with the presence of a mutation, and the common connection of lower-income households being more likely to partake in smoking than higher-income households. This capstone paper will also deliberate beneficial ways to quit smoking, to educate people the risks of smoking and to offer help in accessible, rehabilitee programs. In attempt to bring awareness smoking poses to the state of Indiana, this paper will reveal the damaging effects of the human body externally, internally and environmentally.

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Lung cancer is one of the most common diagnosed cancers leading to cancer-related death worldwide. Around 10-15% of lung cancer patients are non-smokers and majority of lung cancer patients are active smokers. The overall 5-year survival rate remains 18.1% in the United states with little changes despite recent advanced technology and remains worse in the 2nd world countries. Among many types of lung cancer, adenocarcinoma is one of the most common subtypes of non-small cell lung carcinoma (NSCLC), tends to be accounted for 40% of lung cancer cases and tends to form metastases at early stage of lung cancer. Most lung cancers are caused by the exposure of tobacco resulting changes in the genome of susceptible pulmonary cells and increased gene mutations such as epidermal growth factor receptor gene, K-ras gene, and p53 gene. Additionally, tobacco smoking also plays a vital role in the immunological homeostasis with each effect varying from the previous one due to various types of immune cells. Some effects of tobacco smoking to immune cells are weakening the ability of inflammatory cells being recruited into the lungs, decreasing the cell population of inflammatory cells and switching the normal inflammatory response to a harmful one. To sum all, tobacco smoking causes damages in the DNA of epithelial cells and has a huge impact on the immune system that affects the overall contribute to lung carcinogenesis and disease advancement in smokers. An analysis was performed which consisted 11 lung cancer gene-expression datasets that included 1,111 lung adenocarcinomas and 200 normal lung samples. Through this analysis, the compositional patterns of 21 types of immune cells were revealed to have a direct association between the immune cell composition and clinical outcomes (NSCLC). Moreover, two subsets of immune cells, mast cells and CD4+ memory T cells, were discovered and revealed to have opposite outcomes in resting and activated phases as well. Along with the discovery of the two subsets of immune cells, several chemokines and their associated receptors (CXCL 11-CX3CR1) were altered in response to cigarette smoking in smokers than non-smokers. In response to cigarette smoke, mast cells and CD4+ memory T cells switched from a resting phase to an activating phase inducing immune dysfunction in the lung which advances tumor development and progression. Findings from above have given a therapeutic opening for cancer group to prevent tumor invasion and metastasis in lung cancer patients.  From figure 1, lung tumors exhibited different altered pathways between smokers and non-smokers. Differentially expressed genes (DEGs) were further examined of tumor samples that were exposed to tobacco to those from non-smokers. 2,275 DEGs along with 1,298 and 977 genes were up and down regulated in smokers. Pathway enrichment was applied to DEGs as well and found most of the pathways were linked with cell cycle regulation, proliferation, and development categories (NSCLC). Further evaluation was carried by performing a comparison of genes dysregulated in tumor samples between smokers and non-smokers. 1,108 genes as DEGs were identified as tumors and adjacent normal tissues in non-smokers and 1,732 genes in smokers. Only 3 out of 20 pathways were altered in both smokers and non-smokers enriched by DEGs including 2 pathways connected to the immune response and a growth signaling pathway be Rho Family GTPase. The results of non-smokers reveled IL-3 signaling and phagosome formation, which were involved in cell immune response, were particularly enriched in non-smokers indicating the differential pattern of lung carcinogenesis is due to cigarette smoking altering signaling pathways and the tumor microenvironment. 

     

Figure 1. Survival analyses and pathway enrichments for lung cancer patients in ever- and never-smokers with overall survival of lung adenocarcinoma in part A, recurrence-free survival of lung adenocarcinoma in part B and pathways enriched by genes in part C.

In the 1930s and earlier on, with the low percentage of smokers, the cases of lung cancer were minimal. However, studies were conducted and were hypothesized a possible connection between smoking and lung cancer. Through the uprising attention brought by the media, smoking tobacco became common and an exponential growth of lung cancer cases occurred.  According to Gibbons, Byers, and Kurie (2014), “These observations spurred large, definitive studies, along with the development of the appropriate methodology required for epidemiologic studies of chronic diseases, which by the 1950s provided strong epidemiologic evidence for the relationship between the amount of tobacco exposure and risk of cancer, the beneficial effects of cessation, and an association with tumor histology” (p. 3, 4).

In 1959, British Medical Research and a Surgeon General, Dr. Leroy E. Burney, have deemed smoking was the direct cause of lung cancer and an act was adopted which requires health risks labels on all cigarette packages. Consequently, the percentage of current smokers have significantly reduced and approximately 8000,000 deaths have been prevented. In the 1980s, on account of advance technologies and lab tools, studies presented high rates of mutations in known oncogenes such as KRAS and another tumor suppressor known as TP53 in lung tumors. It was found the short arm of chromosome 17 was often deleted after the examination of both primary tumors and other cancerous cell lines along with its point mutations in the rest of TP53 allele (Figure 2). Patients with Li-Fraumeni syndrome were revealed to exhibit the germline TP53 mutations in the absence of tobacco exposure as well as displaying a high susceptibility to develop various types of tumors such as lung carcinoma.

Figure 2. Structure of the p53 protein with functional domains and some sites of posttranslational modifications. The domain consisted N-terminus, a core DNA-binding domain and a C-terminus divided into a tetramerization domain and a CRD domain.

The presence of mutations on KRAS and TP53 created frameshift mutations such as deletion, G to T transversions, and point mutations in the DNA. Extensive exposure of tobacco smoke has demonstrated the increased risks of oncogenic mutations due to consisting more than 60 types of carcinogens including polycyclic aromatic hydrocarbons such as BaP and N-nitrosamines. Chronic exposure of the lung epithelium to these 60 types of carcinogens risks the increased susceptibility to lung tumors due to the synthesis of DNA adducting the oncogenic mutations causing a common case of G to T transversions.  Additionally, in recent studies, current and former smokers displayed a higher exome mutational burden in adenocarcinoma, squamous cell carcinoma, and p53 mutation rate displayed in figure 1 conducted by individual institutions and The Cancer Genome Atlas (TCGA). These studies have revealed a high p53-specific mutation rate leading to a high display rate of mutations in popular regions show in figure 3.

Figure 3. P53 mutation spectrum from the TCGA lung squamous and lung adenocarcinoma datasets representing the percent with p53 mutations versus wild-type p53.

Through studies of tumorigenic DNA viruses, such as simian virus 40 (SV40) and human papilloma virus (HPV), P53 was discovered and revealed to be a target of viral oncoproteins. The interaction between p53 protein and SV40 large T antigen revealed p53 can alter the transformative ability of SV40. The domain structure of p53 consisted N-terminus, a core DNA-binding domain and a C-terminus divided into a tetramerization domain and a CRD domain. It is in later days the exceptional functions of p53 were discovered. In its normal condition, TP53 was found to encode a sequence-specific transcription factor, a protein, of 53kDa in low concentrations with regulation of E3 ubiquitin ligase. In response to stress in its cellular functions, p53 was shown to repair damaged DNA, to arrest cell cycle and to activate cellular apoptosis by stabilizing quickly to localize accumulated protein to the nucleus and transforming capability of transcriptional activity while repressing others (Gibbons, Byers, and Kurie, 2014). Mutant p53, due to the exposure of tobacco, have been shown to cease its typical functions and most important, stopping cell apoptosis causing DNA damage to accumulate in the cells instead of regulating inflammatory signals. Mutant p53 was shown to display frameshift mutations such as chromosomal deletions and point mutation as an activator in the checkpoint. To sum all, most of the amino acids of the protein, p53, were altered which affected its critical role to serve at the core DNA-binding domain and were divided into 2 groups, structural mutants and mutations that affected direct amino-acid contacts shown in figure1. From figure 1, mutational hotspots in lung cancer of gene p53 were revealed to have its core DNA-binding domain to consist of four mutational hotspot regions that were did not exist in its normal condition. With the four mutational hotspots, structural mutants and mutations affected amino-acid contacts were shown to alter its proper function by changing the typical function of protein-protein interactions. This study was concluded by stating tobacco exposure had a huge impact on genomic mutations in lung cancer by its tumor suppressor TP53 being mutated in the process and the vital role of p53 adaptation to this malignant mutation. In addition to a mutated TP53 and its vital role abruptly altered, the exposure of tobacco was revealed to have a huge impact in the overall tumor microenvironment by causing long-lasting inflammation in the lungs, promoting progression of lung cancer in both carcinogen and genetic K-ras-initiated models (Gibbons, Byers, and Kurie, 2014).

Most studies were completed by producing animal models to test the consequences of p53 loss or mutation. Studies found the animal models have developed various types of tumors including lung, sarcoma, and lymphoid malignancies in the first generation when segments of cDNA were electroporated into the embryos to have the animals carry the mutated p53 fragments as well as two copies of WT p53 (Gibbons, Byers, and Kurie, 2014). Furthermore, second generation was created to generate a null p53 allele in homozygous or heterozygous conditions was observed as well. Unexpectedly, the animal models displayed normal development. However, in homozygous conditions, models were found with increased susceptibility to various types of tumors such as sarcomas and T-cell lymphomas. Overall, the animal models, according to Gibbons, Byers, and Kurie (2014), “had enhanced progression of carcinogen-induced malignancies (55), increased susceptibility to radiation-induced sarcomas and lymphomas, and accumulation of chromosomal abnormalities (56)”.

Figure 4. Men’s monthly cigarette expenditures versus per capita monthly expenditure for basic needs, 1997. Cloth, clothing.

The authors and researchers of PATH Canada, Work for a Better Bangladesh and London School of Hygiene and Tropical Medical used available statistics and calculations based on thereon to examine the comparison of the extended cost of tobacco to the potential food and necessities investment in Bangladesh. UNICEF estimated over 200 million children under the age of 5 were malnourished in the lower-income families. With the 200 million children, 6 million of them die annually. From 1995-1996, almost half of the population lived in conditions under the poverty line. In this type of condition, tobacco industry thrived and will continue to do so with the 15 local companies competing in the cigarette market by selling tobacco varieties such as chewing tobacco, bidis and cigarettes. A report was shown BAT (British American Tobacco) Bangladesh profited almost 15.9 million of dollars from these local companies.  According to the researchers of PATH Canada, Work for a Better Bangladesh and London School of Hygiene and Tropical Medical (2001), “Men aged 35–49 years have the highest smoking prevalence at 70.3%2 and smoking prevalence is highest among the poorest”. The findings supported the poorest spend as much as twice on cigarettes than the cost of food, clothing and education combined (Figure 4). This work provided estimation on the number of children could be saved instead of on tobacco expenses. This work stated tobacco expenses have a harmful effect on the quality of life and poverty in Bangladesh as well. Not only does smoking causes significant deterioration in quality of life among the lower-income households, it is also ignored by the government and current smokers. One of the few solutions were created to emphasize the harmful effects of smoking by increasing taxes while helping with the situation of the poor. By reducing the number of smokers in Bangladesh, the quality of life would increase by reducing expanses on non-essential goods. The linking of smoking and lower-income households was also stated in another article, according to Smoking cessation and the cardiovascular patient, “80% of the world’s smokers live in low- and middle-income countries (p, 506). From the same article, smoking tobacco contributed over 60 million deaths and was estimated 1 billion deaths by the end of 21st century globally.

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Not only does smoking relates to lung cancers and tumors, it also contributed declines in cardiovascular disease by developing “endothelia dysfunction, constricting blood vessels, activating platelets, creating a chronic inflammatory state, and causing dyslipidemia” according to Department of Health and Human Services (p. 506-511). The effects of ceasing smoking tobacco have shown instant health benefits such as the reduction of coronary events if stopped for 3 years and heart attacks to mortality if stopped over 3-5 years according to Prochaska, Judith, Benowitz and Neal (2015). Many efforts were exerted to increase the success of tobacco cessation by creating programs all types of smokers can partake in such as cessation pharmacotherapy as an individual, in combination, for a relapse prevention and cytisine treatment. Cessation pharmacotherapy can reduce physical nicotine withdrawal and was examined to hold absolute usefulness and cardiovascular safety when performed on a patient. Clinical practice guidelines have recommended and encouraged the use of cessation pharmacotherapy as well as its recent innovations in combined use, extended use, use in unmotivated-to-quit smokers and treatment matching to better prepare recent smokers with various help. 

Studies have shown smoking tobacco has many harmful effects such as development of lung cancer, mutation in gene p53, a tumor suppressor, and other associated problems such as oral cancer.  Not only is smoking has many health risks, it affects society economically by focusing investment in tobacco instead of food, clothing and education as well. With smoking being a huge topic and very common, researchers have taken the next to stop this epidemic by offering ways to quit smoking, to educate people about the risks and to provide help in accessible, rehabilitee programs. For example, researchers and authors, Prochaska, Judith J.a; Benowitz, Neal L.b wrote an article about prevention and cessation of smoking. This work was supported by receiving a grant from the National Heart, Lung, and Blood Institute to seek the most effectiveness, low cost and alternative substance medications for current smokers. This work also created a reward program through employers to provide quit rates to employees to help stop the tobacco epidemic. This research provides ways lower-income households can participate to spend more money on necessities rather than on tobacco expenses from the article of the economic impact of tobacco consumption on the poor Bangladesh and potentially the United States as well.

Op-Ed

The Destructive Effects of Tobacco Smoking and Ways to Prevent Its Risks

9am on a Friday morning of November 17, I held my breath as I left the double doors of my work from the cigarette smoke my coworkers have inhaled in and out of their chests. My mind raced through the numerous, harmful effects that cigarette possess to the smokers and nonsmokers as we shared the same atmosphere. The ground was covered with a thin layer of cigarette butts as I walked away from the line of smokers and specifically, my manager.

Tobacco smoking has been an ongoing, heated challenge for health workers to highlight the health risks of tobacco exposure for more than 50 years in the United State. This malicious habit continues to increase in numbers and has even been targeting the younger audience as well through cooler designs, commercial exposure and social media. The number of young adults using e-cigarettes has grown exponentially in the last five years and its number of users is even higher than regular cigarettes users. No matter the methods, nicotine in tobacco smoking is addictive and harmful for everyone.

Tobacco consists of many carcinogens that carry several complications of genomic mutations such as the tumor suppressor gene, p53. With the presence of a mutation on gene p53, its vital cellular functions are performed adequately creating high chances of developing cancers early in one’s lifetime. An example of a dysfunctional gene P53 can be seen in lung cancer patients. Lung cancer is one of the most common diagnosed cancer that is caused by the exposure of tobacco resulting changes in the genome of susceptible pulmonary cells and increased gene mutations. Not only is smoking has many health risks, it affects society economically by focusing investment in tobacco instead of food, clothing and education as well. With smoking being a huge topic, researchers have taken the next step to stop this epidemic by offering ways to quit smoking, to educate people about the risks and to provide help in accessible, rehabilitee programs. For example, researchers and authors, Prochaska, Judith J.a; Benowitz, Neal L.b wrote an article about prevention and cessation of smoking. This work was supported by receiving a grant from the National Heart, Lung, and Blood Institute to seek the most effectiveness, low cost and alternative substance medications for current smokers.

References

  1. Gibbons, D. L., Byers, L. A., & Kurie, J. M. (2014). Smoking, p53 Mutation, and Lung Cancer. Molecular Cancer Research : MCR12(1), 3–13. http://doi.org/10.1158/1541-7786.MCR-13-0539
  2. Prochaska, J. J., & Benowitz, N. L. (2015). Smoking Cessation and the Cardiovascular Patient. Current Opinion in Cardiology30(5), 506–511. http://doi.org.proxy.ulib.uits.iu.edu/10.1097/HCO.0000000000000204
  3. Xie, D., Lan, L., Huang, K., Chen, L., Xu, C., Wang, R. … Lu, B. (2014). Association of p53/p21 expression and cigarette smoking with tumor progression and poor prognosis in non-small cell lung cancer patients. Oncology Reports, 32, 2517-2526. https://doi.org/10.3892/or.2014.3538
  4. Efroymson D, Ahmed S, Townsend J, et al. Hungry for tobacco: an analysis of the economic impact of tobacco consumption on the poor in Bangladesh. Tobacco Control. 2001;10(3):212-217. doi:10.1136/tc.10.3.212.
  5. Durazzo, T. C., Mattsson, N., & Weiner, M. W. (2014). Smoking and increased Alzheimer’s disease risk: A review of potential mechanisms. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association10(3 0), S122–S145. http://doi.org.proxy.ulib.uits.iu.edu/10.1016/j.jalz.2014.04.009
  6. Initiative, T. (2018, September 6). truth. Retrieved from Truth Initiative: https://www.thetruth.com/
  7. from Smoking, L. L., & Cessation, A. (2000). A’stages of change’approach to helping patients change behavior. Am Fam Physician61(5), 1409-1416.
  8. Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment Fagerstrom K.-O. (1978) Addictive Behaviors, 3 (3-4), pp. 235-241.
  9.   BMJ, doi:10.1136/bmj.38142.554479.AE (published 22 June 2004)
  10. https://doi.org/10.1136/bmj.282.6259.183 (Published 17 January 1981). Br Med J (Clin Res Ed) 1981;282:183
  11. Li, X., Li, J., Wu, P., Zhou, L., Lu, B., Ying, K., … Liu, P. (2018). Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments. Oncoimmunology, 7(10), e1494677. http://doi.org/10.1080/2162402X.2018.1494677

I have chosen the topic, the effects of smoking, is because it hits a personal spot in my life. I grew in a very strict family where we were taught many important tricks and lessons, but smoking, in particularly, was frowned upon in my family. My parents grew up in the 80s, where everybody smoked, and when the media was encouraging the public to smoke as well. My mother grew up despising her childhood due to the constant smoky presence and made sure her kids did not pick up that bad habit. With that, I grew up knowing smoking was dangerous but not really knowing the facts or effects of smoking. Not knowing the effects that smoking can cause, I wanted to research and to dive deep into this topic. This was one of the factors I’ve chose for this topic, but more importantly, the greatest factor of all, was because I am surrounded with many co-workers that smoke, specifically, my manager.

This topic matters in a bigger sense due to wanting to bring awareness of the harmful effects smoking tobacco can cause and even if this only change one person, I want that one person to know I care enough to dedicate an entire research paper because of them. I want that one person to know there is reachable help they can receive if one is ready to cease smoking. This will allow them to live a healthier and longer life with their family. This act of dedication, I hope, will provide facts and information others need when they want to understand the addictive traits and harmful actions smoking possess. This capstone paper covers the damaging effects of the human body externally, internally and environmentally. 

This research project was an excellent exercise for undergraduate students to practice the kind of research that was required to write out an extensive topic. This activity required the students to research the topic, to use scientific articles, and more importantly, to dedicate time to write out the paper in an insightful way. The several meetings that were required throughout the semester really encouraged me to be more passionate in this topic as well as more diligent in my researching ability. This activity provided helpful experience for students to gain skills for future employment opportunities as well. After this capstone project, I feel more confident in my researching ability to write out a well thought out paper and to obtain a future employment in the biology field.

The next steps in this field that need to be done to advance the treatment, prognosis or management of smoking are to target the younger audience that are participating in this act. There are various ways younger audience are manipulated by the smoking industry to obtain an addiction such as vaping, chewing and smoking nicotine. To this, the government should intervene and disallow the sale of the tobacco to those who are under 21 and the school systems should confiscate all gadgets that are involved in tobacco usage. The school systems should require the students to attend a class to warn the students the harmful effects of smoking tobacco. The class should be mandatory and if not taken, the student cannot graduate. Finally, I hope recommendations like the previous ones that were listed will lower the percentage of smokers in the overall state of Indiana.   

Lung Cancer, p53 mutation with SV40, and the Connection Between Smoking and Lower-Income Households

According to Gibbons, Byers, and Kurie (2014), “Tobacco exposure is the leading cause of cancers involving the oral cavity, conductive airways, and the lung” (p. 3). Under the same article, the challenge to highlight the health risks of tobacco exposure has been an active topic for more than 50 years in the United States. Tobacco consists many carcinogens that carry several complications of genomic mutations such as the tumor suppressor gene, p53. With the presence of a mutation on gene p53, its vital cellular functions are performed adequately creating high chances of developing cancers early in one’s lifetime. This capstone paper will include the linking lung cancer and genetic mutations with the human lungs after the exposure of tobacco, cellular roles of p53 under typical and altered conditions with the presence of a mutation, and the common connection of lower-income households being more likely to partake in smoking than higher-income households. This capstone paper will also deliberate beneficial ways to quit smoking, to educate people the risks of smoking and to offer help in accessible, rehabilitee programs. In attempt to bring awareness smoking poses to the state of Indiana, this paper will reveal the damaging effects of the human body externally, internally and environmentally.

Lung cancer is one of the most common diagnosed cancers leading to cancer-related death worldwide. Around 10-15% of lung cancer patients are non-smokers and majority of lung cancer patients are active smokers. The overall 5-year survival rate remains 18.1% in the United states with little changes despite recent advanced technology and remains worse in the 2nd world countries. Among many types of lung cancer, adenocarcinoma is one of the most common subtypes of non-small cell lung carcinoma (NSCLC), tends to be accounted for 40% of lung cancer cases and tends to form metastases at early stage of lung cancer. Most lung cancers are caused by the exposure of tobacco resulting changes in the genome of susceptible pulmonary cells and increased gene mutations such as epidermal growth factor receptor gene, K-ras gene, and p53 gene. Additionally, tobacco smoking also plays a vital role in the immunological homeostasis with each effect varying from the previous one due to various types of immune cells. Some effects of tobacco smoking to immune cells are weakening the ability of inflammatory cells being recruited into the lungs, decreasing the cell population of inflammatory cells and switching the normal inflammatory response to a harmful one. To sum all, tobacco smoking causes damages in the DNA of epithelial cells and has a huge impact on the immune system that affects the overall contribute to lung carcinogenesis and disease advancement in smokers. An analysis was performed which consisted 11 lung cancer gene-expression datasets that included 1,111 lung adenocarcinomas and 200 normal lung samples. Through this analysis, the compositional patterns of 21 types of immune cells were revealed to have a direct association between the immune cell composition and clinical outcomes (NSCLC). Moreover, two subsets of immune cells, mast cells and CD4+ memory T cells, were discovered and revealed to have opposite outcomes in resting and activated phases as well. Along with the discovery of the two subsets of immune cells, several chemokines and their associated receptors (CXCL 11-CX3CR1) were altered in response to cigarette smoking in smokers than non-smokers. In response to cigarette smoke, mast cells and CD4+ memory T cells switched from a resting phase to an activating phase inducing immune dysfunction in the lung which advances tumor development and progression. Findings from above have given a therapeutic opening for cancer group to prevent tumor invasion and metastasis in lung cancer patients.  From figure 1, lung tumors exhibited different altered pathways between smokers and non-smokers. Differentially expressed genes (DEGs) were further examined of tumor samples that were exposed to tobacco to those from non-smokers. 2,275 DEGs along with 1,298 and 977 genes were up and down regulated in smokers. Pathway enrichment was applied to DEGs as well and found most of the pathways were linked with cell cycle regulation, proliferation, and development categories (NSCLC). Further evaluation was carried by performing a comparison of genes dysregulated in tumor samples between smokers and non-smokers. 1,108 genes as DEGs were identified as tumors and adjacent normal tissues in non-smokers and 1,732 genes in smokers. Only 3 out of 20 pathways were altered in both smokers and non-smokers enriched by DEGs including 2 pathways connected to the immune response and a growth signaling pathway be Rho Family GTPase. The results of non-smokers reveled IL-3 signaling and phagosome formation, which were involved in cell immune response, were particularly enriched in non-smokers indicating the differential pattern of lung carcinogenesis is due to cigarette smoking altering signaling pathways and the tumor microenvironment. 

     

Figure 1. Survival analyses and pathway enrichments for lung cancer patients in ever- and never-smokers with overall survival of lung adenocarcinoma in part A, recurrence-free survival of lung adenocarcinoma in part B and pathways enriched by genes in part C.

In the 1930s and earlier on, with the low percentage of smokers, the cases of lung cancer were minimal. However, studies were conducted and were hypothesized a possible connection between smoking and lung cancer. Through the uprising attention brought by the media, smoking tobacco became common and an exponential growth of lung cancer cases occurred.  According to Gibbons, Byers, and Kurie (2014), “These observations spurred large, definitive studies, along with the development of the appropriate methodology required for epidemiologic studies of chronic diseases, which by the 1950s provided strong epidemiologic evidence for the relationship between the amount of tobacco exposure and risk of cancer, the beneficial effects of cessation, and an association with tumor histology” (p. 3, 4).

In 1959, British Medical Research and a Surgeon General, Dr. Leroy E. Burney, have deemed smoking was the direct cause of lung cancer and an act was adopted which requires health risks labels on all cigarette packages. Consequently, the percentage of current smokers have significantly reduced and approximately 8000,000 deaths have been prevented. In the 1980s, on account of advance technologies and lab tools, studies presented high rates of mutations in known oncogenes such as KRAS and another tumor suppressor known as TP53 in lung tumors. It was found the short arm of chromosome 17 was often deleted after the examination of both primary tumors and other cancerous cell lines along with its point mutations in the rest of TP53 allele (Figure 2). Patients with Li-Fraumeni syndrome were revealed to exhibit the germline TP53 mutations in the absence of tobacco exposure as well as displaying a high susceptibility to develop various types of tumors such as lung carcinoma.

Figure 2. Structure of the p53 protein with functional domains and some sites of posttranslational modifications. The domain consisted N-terminus, a core DNA-binding domain and a C-terminus divided into a tetramerization domain and a CRD domain.

The presence of mutations on KRAS and TP53 created frameshift mutations such as deletion, G to T transversions, and point mutations in the DNA. Extensive exposure of tobacco smoke has demonstrated the increased risks of oncogenic mutations due to consisting more than 60 types of carcinogens including polycyclic aromatic hydrocarbons such as BaP and N-nitrosamines. Chronic exposure of the lung epithelium to these 60 types of carcinogens risks the increased susceptibility to lung tumors due to the synthesis of DNA adducting the oncogenic mutations causing a common case of G to T transversions.  Additionally, in recent studies, current and former smokers displayed a higher exome mutational burden in adenocarcinoma, squamous cell carcinoma, and p53 mutation rate displayed in figure 1 conducted by individual institutions and The Cancer Genome Atlas (TCGA). These studies have revealed a high p53-specific mutation rate leading to a high display rate of mutations in popular regions show in figure 3.

Figure 3. P53 mutation spectrum from the TCGA lung squamous and lung adenocarcinoma datasets representing the percent with p53 mutations versus wild-type p53.

Through studies of tumorigenic DNA viruses, such as simian virus 40 (SV40) and human papilloma virus (HPV), P53 was discovered and revealed to be a target of viral oncoproteins. The interaction between p53 protein and SV40 large T antigen revealed p53 can alter the transformative ability of SV40. The domain structure of p53 consisted N-terminus, a core DNA-binding domain and a C-terminus divided into a tetramerization domain and a CRD domain. It is in later days the exceptional functions of p53 were discovered. In its normal condition, TP53 was found to encode a sequence-specific transcription factor, a protein, of 53kDa in low concentrations with regulation of E3 ubiquitin ligase. In response to stress in its cellular functions, p53 was shown to repair damaged DNA, to arrest cell cycle and to activate cellular apoptosis by stabilizing quickly to localize accumulated protein to the nucleus and transforming capability of transcriptional activity while repressing others (Gibbons, Byers, and Kurie, 2014). Mutant p53, due to the exposure of tobacco, have been shown to cease its typical functions and most important, stopping cell apoptosis causing DNA damage to accumulate in the cells instead of regulating inflammatory signals. Mutant p53 was shown to display frameshift mutations such as chromosomal deletions and point mutation as an activator in the checkpoint. To sum all, most of the amino acids of the protein, p53, were altered which affected its critical role to serve at the core DNA-binding domain and were divided into 2 groups, structural mutants and mutations that affected direct amino-acid contacts shown in figure1. From figure 1, mutational hotspots in lung cancer of gene p53 were revealed to have its core DNA-binding domain to consist of four mutational hotspot regions that were did not exist in its normal condition. With the four mutational hotspots, structural mutants and mutations affected amino-acid contacts were shown to alter its proper function by changing the typical function of protein-protein interactions. This study was concluded by stating tobacco exposure had a huge impact on genomic mutations in lung cancer by its tumor suppressor TP53 being mutated in the process and the vital role of p53 adaptation to this malignant mutation. In addition to a mutated TP53 and its vital role abruptly altered, the exposure of tobacco was revealed to have a huge impact in the overall tumor microenvironment by causing long-lasting inflammation in the lungs, promoting progression of lung cancer in both carcinogen and genetic K-ras-initiated models (Gibbons, Byers, and Kurie, 2014).

Most studies were completed by producing animal models to test the consequences of p53 loss or mutation. Studies found the animal models have developed various types of tumors including lung, sarcoma, and lymphoid malignancies in the first generation when segments of cDNA were electroporated into the embryos to have the animals carry the mutated p53 fragments as well as two copies of WT p53 (Gibbons, Byers, and Kurie, 2014). Furthermore, second generation was created to generate a null p53 allele in homozygous or heterozygous conditions was observed as well. Unexpectedly, the animal models displayed normal development. However, in homozygous conditions, models were found with increased susceptibility to various types of tumors such as sarcomas and T-cell lymphomas. Overall, the animal models, according to Gibbons, Byers, and Kurie (2014), “had enhanced progression of carcinogen-induced malignancies (55), increased susceptibility to radiation-induced sarcomas and lymphomas, and accumulation of chromosomal abnormalities (56)”.

Figure 4. Men’s monthly cigarette expenditures versus per capita monthly expenditure for basic needs, 1997. Cloth, clothing.

The authors and researchers of PATH Canada, Work for a Better Bangladesh and London School of Hygiene and Tropical Medical used available statistics and calculations based on thereon to examine the comparison of the extended cost of tobacco to the potential food and necessities investment in Bangladesh. UNICEF estimated over 200 million children under the age of 5 were malnourished in the lower-income families. With the 200 million children, 6 million of them die annually. From 1995-1996, almost half of the population lived in conditions under the poverty line. In this type of condition, tobacco industry thrived and will continue to do so with the 15 local companies competing in the cigarette market by selling tobacco varieties such as chewing tobacco, bidis and cigarettes. A report was shown BAT (British American Tobacco) Bangladesh profited almost 15.9 million of dollars from these local companies.  According to the researchers of PATH Canada, Work for a Better Bangladesh and London School of Hygiene and Tropical Medical (2001), “Men aged 35–49 years have the highest smoking prevalence at 70.3%2 and smoking prevalence is highest among the poorest”. The findings supported the poorest spend as much as twice on cigarettes than the cost of food, clothing and education combined (Figure 4). This work provided estimation on the number of children could be saved instead of on tobacco expenses. This work stated tobacco expenses have a harmful effect on the quality of life and poverty in Bangladesh as well. Not only does smoking causes significant deterioration in quality of life among the lower-income households, it is also ignored by the government and current smokers. One of the few solutions were created to emphasize the harmful effects of smoking by increasing taxes while helping with the situation of the poor. By reducing the number of smokers in Bangladesh, the quality of life would increase by reducing expanses on non-essential goods. The linking of smoking and lower-income households was also stated in another article, according to Smoking cessation and the cardiovascular patient, “80% of the world’s smokers live in low- and middle-income countries (p, 506). From the same article, smoking tobacco contributed over 60 million deaths and was estimated 1 billion deaths by the end of 21st century globally.

Not only does smoking relates to lung cancers and tumors, it also contributed declines in cardiovascular disease by developing “endothelia dysfunction, constricting blood vessels, activating platelets, creating a chronic inflammatory state, and causing dyslipidemia” according to Department of Health and Human Services (p. 506-511). The effects of ceasing smoking tobacco have shown instant health benefits such as the reduction of coronary events if stopped for 3 years and heart attacks to mortality if stopped over 3-5 years according to Prochaska, Judith, Benowitz and Neal (2015). Many efforts were exerted to increase the success of tobacco cessation by creating programs all types of smokers can partake in such as cessation pharmacotherapy as an individual, in combination, for a relapse prevention and cytisine treatment. Cessation pharmacotherapy can reduce physical nicotine withdrawal and was examined to hold absolute usefulness and cardiovascular safety when performed on a patient. Clinical practice guidelines have recommended and encouraged the use of cessation pharmacotherapy as well as its recent innovations in combined use, extended use, use in unmotivated-to-quit smokers and treatment matching to better prepare recent smokers with various help. 

Studies have shown smoking tobacco has many harmful effects such as development of lung cancer, mutation in gene p53, a tumor suppressor, and other associated problems such as oral cancer.  Not only is smoking has many health risks, it affects society economically by focusing investment in tobacco instead of food, clothing and education as well. With smoking being a huge topic and very common, researchers have taken the next to stop this epidemic by offering ways to quit smoking, to educate people about the risks and to provide help in accessible, rehabilitee programs. For example, researchers and authors, Prochaska, Judith J.a; Benowitz, Neal L.b wrote an article about prevention and cessation of smoking. This work was supported by receiving a grant from the National Heart, Lung, and Blood Institute to seek the most effectiveness, low cost and alternative substance medications for current smokers. This work also created a reward program through employers to provide quit rates to employees to help stop the tobacco epidemic. This research provides ways lower-income households can participate to spend more money on necessities rather than on tobacco expenses from the article of the economic impact of tobacco consumption on the poor Bangladesh and potentially the United States as well.

Op-Ed

The Destructive Effects of Tobacco Smoking and Ways to Prevent Its Risks

9am on a Friday morning of November 17, I held my breath as I left the double doors of my work from the cigarette smoke my coworkers have inhaled in and out of their chests. My mind raced through the numerous, harmful effects that cigarette possess to the smokers and nonsmokers as we shared the same atmosphere. The ground was covered with a thin layer of cigarette butts as I walked away from the line of smokers and specifically, my manager.

Tobacco smoking has been an ongoing, heated challenge for health workers to highlight the health risks of tobacco exposure for more than 50 years in the United State. This malicious habit continues to increase in numbers and has even been targeting the younger audience as well through cooler designs, commercial exposure and social media. The number of young adults using e-cigarettes has grown exponentially in the last five years and its number of users is even higher than regular cigarettes users. No matter the methods, nicotine in tobacco smoking is addictive and harmful for everyone.

Tobacco consists of many carcinogens that carry several complications of genomic mutations such as the tumor suppressor gene, p53. With the presence of a mutation on gene p53, its vital cellular functions are performed adequately creating high chances of developing cancers early in one’s lifetime. An example of a dysfunctional gene P53 can be seen in lung cancer patients. Lung cancer is one of the most common diagnosed cancer that is caused by the exposure of tobacco resulting changes in the genome of susceptible pulmonary cells and increased gene mutations. Not only is smoking has many health risks, it affects society economically by focusing investment in tobacco instead of food, clothing and education as well. With smoking being a huge topic, researchers have taken the next step to stop this epidemic by offering ways to quit smoking, to educate people about the risks and to provide help in accessible, rehabilitee programs. For example, researchers and authors, Prochaska, Judith J.a; Benowitz, Neal L.b wrote an article about prevention and cessation of smoking. This work was supported by receiving a grant from the National Heart, Lung, and Blood Institute to seek the most effectiveness, low cost and alternative substance medications for current smokers.

References

  1. Gibbons, D. L., Byers, L. A., & Kurie, J. M. (2014). Smoking, p53 Mutation, and Lung Cancer. Molecular Cancer Research : MCR12(1), 3–13. http://doi.org/10.1158/1541-7786.MCR-13-0539
  2. Prochaska, J. J., & Benowitz, N. L. (2015). Smoking Cessation and the Cardiovascular Patient. Current Opinion in Cardiology30(5), 506–511. http://doi.org.proxy.ulib.uits.iu.edu/10.1097/HCO.0000000000000204
  3. Xie, D., Lan, L., Huang, K., Chen, L., Xu, C., Wang, R. … Lu, B. (2014). Association of p53/p21 expression and cigarette smoking with tumor progression and poor prognosis in non-small cell lung cancer patients. Oncology Reports, 32, 2517-2526. https://doi.org/10.3892/or.2014.3538
  4. Efroymson D, Ahmed S, Townsend J, et al. Hungry for tobacco: an analysis of the economic impact of tobacco consumption on the poor in Bangladesh. Tobacco Control. 2001;10(3):212-217. doi:10.1136/tc.10.3.212.
  5. Durazzo, T. C., Mattsson, N., & Weiner, M. W. (2014). Smoking and increased Alzheimer’s disease risk: A review of potential mechanisms. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association10(3 0), S122–S145. http://doi.org.proxy.ulib.uits.iu.edu/10.1016/j.jalz.2014.04.009
  6. Initiative, T. (2018, September 6). truth. Retrieved from Truth Initiative: https://www.thetruth.com/
  7. from Smoking, L. L., & Cessation, A. (2000). A’stages of change’approach to helping patients change behavior. Am Fam Physician61(5), 1409-1416.
  8. Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment Fagerstrom K.-O. (1978) Addictive Behaviors, 3 (3-4), pp. 235-241.
  9.   BMJ, doi:10.1136/bmj.38142.554479.AE (published 22 June 2004)
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  11. Li, X., Li, J., Wu, P., Zhou, L., Lu, B., Ying, K., … Liu, P. (2018). Smoker and non-smoker lung adenocarcinoma is characterized by distinct tumor immune microenvironments. Oncoimmunology, 7(10), e1494677. http://doi.org/10.1080/2162402X.2018.1494677

I have chosen the topic, the effects of smoking, is because it hits a personal spot in my life. I grew in a very strict family where we were taught many important tricks and lessons, but smoking, in particularly, was frowned upon in my family. My parents grew up in the 80s, where everybody smoked, and when the media was encouraging the public to smoke as well. My mother grew up despising her childhood due to the constant smoky presence and made sure her kids did not pick up that bad habit. With that, I grew up knowing smoking was dangerous but not really knowing the facts or effects of smoking. Not knowing the effects that smoking can cause, I wanted to research and to dive deep into this topic. This was one of the factors I’ve chose for this topic, but more importantly, the greatest factor of all, was because I am surrounded with many co-workers that smoke, specifically, my manager.

This topic matters in a bigger sense due to wanting to bring awareness of the harmful effects smoking tobacco can cause and even if this only change one person, I want that one person to know I care enough to dedicate an entire research paper because of them. I want that one person to know there is reachable help they can receive if one is ready to cease smoking. This will allow them to live a healthier and longer life with their family. This act of dedication, I hope, will provide facts and information others need when they want to understand the addictive traits and harmful actions smoking possess. This capstone paper covers the damaging effects of the human body externally, internally and environmentally. 

This research project was an excellent exercise for undergraduate students to practice the kind of research that was required to write out an extensive topic. This activity required the students to research the topic, to use scientific articles, and more importantly, to dedicate time to write out the paper in an insightful way. The several meetings that were required throughout the semester really encouraged me to be more passionate in this topic as well as more diligent in my researching ability. This activity provided helpful experience for students to gain skills for future employment opportunities as well. After this capstone project, I feel more confident in my researching ability to write out a well thought out paper and to obtain a future employment in the biology field.

The next steps in this field that need to be done to advance the treatment, prognosis or management of smoking are to target the younger audience that are participating in this act. There are various ways younger audience are manipulated by the smoking industry to obtain an addiction such as vaping, chewing and smoking nicotine. To this, the government should intervene and disallow the sale of the tobacco to those who are under 21 and the school systems should confiscate all gadgets that are involved in tobacco usage. The school systems should require the students to attend a class to warn the students the harmful effects of smoking tobacco. The class should be mandatory and if not taken, the student cannot graduate. Finally, I hope recommendations like the previous ones that were listed will lower the percentage of smokers in the overall state of Indiana.   

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