Genetic+Mutations+Linked+to+Smoking+Cigarettes

=**Introduction**= toc

Many studies have previously been done that show that smoking cigarettes correlates with an increased risk of getting cancer. Until more recently with developing technology scientists really did not have the best understanding of what cigarettes actually do to the body. Through the process of [|genome sequencing] of large groups of smokers and non-smokers with cancer, scientists noticed a difference in the number of mutations of the [|TP53] gene, the[| KRAS] gene, and passenger genes in cancerous lung and pancreatic cells. These are mutations that result in [|lung cancer] and [|pancreatic cancer], both of which are leading causes of death in today's world. Understanding these mutations and their source can help scientists potentially find cures and can give people a better understanding of what kinds of preventative actions they can take to decrease their risk of getting cancer. Previous studies have just took groups of people with cancer and compared the number of people with cancer who smoked at one point or another if not frequently during their life and compared it to the number of people with cancer that didn’t smoke. While these types of studies did show that there was a correlation between smoking and cancer there wasn’t a good understanding of what smoking cigarettes truly does to the body. Further studies have gone to show that smoking cigarettes directly cause pancreatic and lung cancer, taking a look into genetic mutations from smoking.

**TP53 Mutations**
The TP53 is a gene contains p53 proteins that are responsible for [|tumor suppression]. This tumor suppressor stops damaged cells from proliferating, triggers cell death, and thus prevents cancer formation (2). When there is mutations within the TP53 genes more cancerous cells are typically present. Through studies of different cancer genomes scientists have been able to correlate TP53 gene mutations with smoking status. To do this scientists take groups of about 100 – 200 patients with the same type of cancer, some smokers and some non-smokers, and sequence the proteins from every patient’s cancerous cells. Based off of the [|somatic changes] genetic changes and smoking status of the patient scientists have been able to correlate specific genetic changes to smoking. To do this they measured the frequency of the mutations in smokers and nonsmokers while also accounting for other factors such as age and gender (9). These studies have shown a net increase in the overall number of genetic mutations of the TP53 gene in people that smoked compared to non-smokers with the same type of cancer. These types of mutations are typically found in types of lung cancer as well as in types of pancreatic cancers. This leads to the conclusion that an increased number of TP53 mutations leads to an increased risk at getting pancreatic and lung cancer. Even more interesting from studies of cancerous cells scientists have found there to be a different TP53 mutation spectrum in smokers versus non-smokers. The TP53 is vital to fighting tumors and smoking cigarettes has been shown to increase the number of mutations of this gene as well as some others.

**KRAS Mutations**
The KRAS gene is responsible for tissue signaling within the human body. This gene can lead to the early development of tumors as they can activate cell growth. Mutations in this gene can lead to the transformation of various proteins that result in various [|malignancies]. Through similar studies as done to study the TP53 gene scientists have used genetic sequencing, taking cancerous cells from patients to also study KRAS mutations. Comparing somatic changes in the KRAS gene between smokers and non-smokers scientists were also able to correlate KRAS mutations with moking. Scientists have shown through these studies that [|activating point mutations] in the KRAS gene are more common in [|adenocarcinomas] of the lung resected from smokers than they are in adenocarcinomas from nonsmokers (2). For instance one study showed significantly more KRAS mutations in lung adenocarcinomas obtained from current smokers (30%) and former smokers (32%) which was compared to lung adenocarcinomas obtained from non-smokers (7%) (10). With the KRAS gene being so vital to activating growth of cells it is important to avoid these mutations to maintain ones health. With an increase in smoking habits there has been a proven increased risk of developing KRAS mutations that lead to tumors and different types of cancer.

**Pancreatic Cancer Mutations**
Pancreatic cancer is one of the most lethal cancers that is caused by mutations in the KRAS and TP53 genes. Cigarette smoking has been proven to increase these mutations, resulting in a doubled risk of obtaining pancreatic cancer (2). Studies showed that along with an increase in the KRAS and TP53 mutations there was also a large increase in the number of passenger genes but there has been difficulty relating these passenger mutations to a characteristic profile. Scientists have been able to use the data found on passenger mutations to link smoking to mutation rates showing that with an increase in smoking status increases the rate at which genetic mutations occur. There is still much more to be researched as far as some of the less prominent passenger mutations and how smoking has an effect on them. As for now it is known that smoking increases the risk of the number of genetic mutations present in pancreatic cancerous cells.

**Lung Cancer Mutations**
As expected, even more predominate than pancreatic cancer mutations, smoking causes many different gene mutations that lead to lung cancer including the KRAS and TP53 mutations. Lung cancer, which has also been proven to be one of the most lethal cancers, accounts for approximately 28% of the cancer deaths (9). The studies that correlated genetic mutations in lung cancers were similar to that of the studies with the pancreatic cancers. They involved taking a group of patients of whom all had lung cancer, some of which were smokers, and some of which non-smokers. Again genome sequencing of the genes found in the lung cancers was used. Similarly the studies showed an increase in many passenger mutations within the cancerous lung cells of smokers compared to non-smokers. Again a much higher mutation rate was shown with the passenger mutations. Some of the driving mutations in the cancerous lung cells were comparable between smokers and non-smokers presumably because these mutations had to exist for the cancer to be present in the first place. This means that while smoking is not always the cause of these mutations scientists have shown it to cause the mutations to happen much more rapidly.

=**Conclusion**=

It is known that smoking tobacco and cigarettes can have negative [|health effects]. With the use of genome sequencing and statistical analysis scientists have been able to better understand the effects that smoking has on the human body. Through analysis of different types of cancer present among smokers and non-smokers and with the use of genome sequencing studies have shown that smoking does in fact increase the number mutations in the TP53 gene, KRAS gene, and passenger genes that are present pancreatic and lung cancers. More specifically scientists have been able to prove through their research direct mutation patterns that can be caused by smoking. This can be shown by the difference in the mutation of the TP53 and KRAS gene mutations among smokers and non-smokers as well as by the high frequency of passenger gene mutations in different cancers among smokers. Scientists have begun to better understand what genes smoking directly affect. With these cancers being a predominant factor leading to deaths it is important to keep researching to fully understand the cause of the genetic mutations causing these cancers so that one day they may be able to be prevented.

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