3 minutes

 

Why do people smoke? Most people know smoking can dramatically shorten your lifespan and give you a whole host of terrible cancers, yet many people still smoke. Whether they are smoking to relieve some stress and pressure, control their weight or young people want to act mature, choosing to smoke can result in harsh consequences.

The most common cancer for smoking is non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of all lung cancers and is divided into three subtypes: Adenocarcinoma (AC), Squamous Cell Carcinoma (SCC), and Large-cell Carcinoma. The different types of NSCLC develop in different locations within the lungs. Adenocarcinoma makes up about 40% of NSCLC. It is developed in the peripheral portions of the lung. Squamous Cell Carcinoma makes up about 30% of NSCLC. It tends to occur close to the main bronchus and can cause obstruction of the airways. Finally, Large-cell Carcinoma makes up about 10% of NSCLC. It is located either central or peripheral portions of the lung and it can rapidly grow along the airways of the respiratory system.

Distribution of lung cancers. http://www.medicinenet.com/lung_cancer/page7.htm

Human bodies contain tumor protein 53 (TP53). TP53 is a protein encoded for cell cycle arrest, DNA repair, and apoptosis. TP53 plays an important role as a tumor suppressor that conserves stability by preventing genome mutation. However, TP53 appears to be the most common target to be mutated in human cancer. Mutated TP53makes up about 50% of NSCLC, containing both alleles mutated. The missense mutations are responsible of 80% of TP53 gene mutations. Mutation to TP53 hinder its normal tumor suppressing capabilities, thus DNA damage remains unchecked, faulty cells proceed through the cell cycle and apoptosis is evaded. This creates a genetic condition in which the cell is more susceptible to further mutations. When TP53 is mutated it gains new oncogenic activities called “gain-of-function” (GOF)activities, which can contribute actively to various stages of tumor progression and to increased resistance to anticancer treatments. GOF activities of mutated TP53 are utilized by gene regulation or abnormal protein interaction.

TP53 is considered to be the most common target when it comes to smoking. Comparing between patients with lung cancer associated with smoking and patients who never smoked, the latter have a lower chance of having TP53 mutated (8%-47%) than the formal (26%-71%). Mutated TP53 are different between smokers and non-smokers with an excess of G to T transversions in smoking-associated cancers. Polycyclic aromatic hydrocarbons (PAHs)are responsible for G to T transversion. PAH contains large portions of prominent carcinogens that can produce predominantly this type of mutation. With the strand-specific repair of guanine-benzo[α]pyrene adducts, DNA sequence-specific distribution of G to T transversion correlates very well. Benzo[α]pyrene is the member of the PAH class, and Benzo[α]pyrene diol epoxide (BPDE) is the main metabolite of Benzo[α]pyrene, one of the carcinogens present in high quantity in tobacco smoke. Comparingthe distribution of G to T transversion for smokers and non-smokers, the location of the G to T transversion for non-smokers are at codon148, 158, 242, and four at 249. For smokers, it’s located at codon 57, 158, 245, 248, 249 and 273. The binding sites of all codons are suitable for BPDE and other PAHs except for codon 249. What makes codon 249 interesting is not only is it not a site for PAH adduct formation, it is over-represented in non-smokers.

The bad news for patients with tumors bearing a TP53 mutation is that basics treatments may not work as effectively. Depending on the type of cancer a person has, and whether their tumor is missing a TP53 gene or has a mutated one -their cancer may be more resistant to certain treatments such as radiation or specific chemotherapy compounds. There is one case that radiotherapy3, a special equipment to send high doses of radiation to the cancer cells, was used but it had 20% successful rate. There is a preclinical study showing that the doctor can restore TP53 gene which activate apoptosis, thus destroying cancerous cells. They achieved this through genetically engineered viruses known as viral vectors. Transportation of DNA is infectious so the doctors modified their genetic code to prevent the viruses from replicating.

The best way for smokers to reduce their risk of cancer, and improve their overall health, is to stop smoking completely. That, of course, is extremely difficult to do because of nicotine addiction. There have been many ways to help people stop smoking; one of the common ways is to take up vaping. E-cigarette helps smokers switch from more harmful tobacco cigarettes. Well… That’s debatable. Some are bad and some are good. What about nicotine? That works as well but don’t put too much hope on nicotine. It’s harmless but highly addictive unless taken in large quantities. To me, I never smoked in my entire life so I have no opinion. But, if you have a hard time quitting smoking, I recommend seeing a counselor or take a prescription medication. Your life is more important than smoking. Be smart.

 

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Reference

  1. Mogi, A., Kuwano, H. TP53 Mutations in Nonsmall Cell Lung Cancer. Journal of Biomedicine and Biotechnology. 2011. Page 9.
  2. Pfeifer, G. P., Hainaut, P. On the origin of G to T transversions in lung cancer. Mutation Research. 2003. 526: 39-43.
  3. Roth, J. A., Swisher, S. G., Meyn, R. E. p53 Tumor Suppressor Gene Therapy for Cancer. Cancer Network. 1999.