27E93C3A-83B9-4595-91CE-57506165869F Created with sketchtool. Smoking Clears the Path for Lung Cancer

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  Last updated October 4, 2017 at 8:30 am

The link between smoking and lung cancer is well-established, but that doesn’t mean that research into how the connection works should slow down. Recent research looked at the effects of smoking on lung cells before cancer develops. 

Stop anyone on the street, and they will probably tell you they personally know someone who has been affected by cancer. In Australia, cancer is the leading cause of death – by the time you reach the age of 85, you will have a 1 in 2 chance of being diagnosed with some form of cancer. Every year, researchers make new strides in cancer research diagnoses in the hopes that we will eventually find a cure. One such area of research is oncogenomics, which involves the identification of tumor suppression genes to develop more accurate methods of cancer diagnosis, targeted therapies and predicting the outcomes.

The latest research from the USA shows that smoking cigarettes switches off the genes in healthy lung cells that protect them from becoming cancerous. They have shown that by smoking, you’re effectively priming your lung cells to develop cancer – but the good news is that it’s reversible. This mechanism that may shed light on how genetic and epigenetic factors work in parallel to produce the complex process of cancer formation and give the hope that certain types of cancers can be reversed within a certain time frame.

Currently, it is understood that cancer can arise from genetic abnormalities, where the DNA sequence of a gene is altered (or mutated), and epigenetic changes, which do not involve the alteration of the DNA sequence but rather the modification of the gene expression. Until now, however, it was not fully understood how exactly these molecular events worked together to form cancerous tumours.

In a new study conducted by researchers from the John Hopkins University School of Medicine, healthy human lung cells were exposed to cigarette smoke condensate (a concentrated mix consisting of the particles which make up cigarette smoke excluding water or nicotine) to evaluate the effects of continuous exposure to concentrations of cigarette smoke on the epigenome – the network of chemical compounds which tell a cell’s DNA what to do.  After 10 to 15 months of exposure, equivalent to 20 to 30 years of smoking, they noticed a number of significant changes in the cells. For reference, the average yield of tar or concentrate is 11 mg/cigarette for the research cigarette used (though this varies based on the model/brand). In this experiment, the concentration used was 5 μg/ml and 10 μg/ml. 

Most notably was the evidence that the genes in healthy cells which help protect them from becoming cancerous were effectively being switched off, rendering them susceptible to cancer formation when the mutant oncogene (a gene which causes dying cells to proliferate instead) KRASV12 was expressed. This behavior starkly contrasts with that of healthy cells; while the same behaviours leading to cancer formation were still seen in the healthy cells, the frequency of such occurrences was much lower and showed far more coordination than in the cells exposed to cigarette smoke. When the researchers introduced the KRASV12 mutation into cells with epigenetic alterations, they found that cells exposed to cigarette smoke for 6 months did not become cancerous whereas cells exposed for 10 months did, hinting that it took a certain length of time for the cells to become vulnerable to the mutation.

The researchers also noticed that these changes occurred without the presence of any detectable DNA mutations. Rather, exposure to the concentrated cigarette smoke led to extensive changes in DNA methylation, the process in which the activity of the DNA sequence is altered via the addition of a methyl group to the DNA molecule. What this means is that the key cause of cancer formation in this particular scenario was not DNA mutations, but rather epigenetics.

This hypothesis was further solidified by the presence of chemical markers which indicate the silencing of the tumour suppressing genes; these same markers are found in lung adenocarcinoma and squamous cell carcinoma, both common forms of cancer.

According to senior author Stephen Baylin, “When you’re smoking, you are building up a substrate of epigenetic changes that we hypothesize are increasing your mathematics for developing lung cancer, because if you’re not a smoker, your risk of lung cancer is very low.” In other words, in addition to the higher risk of genetic mutations that comes with smoking, your risk of getting lung cancer will be even greater due to the non-genetic abnormalities in your cells caused by the cigarette smoke.

First author Michelle Vaz points out that there is scope for future research in potentially reversing lung cancer in patients. “This work suggests the possibility that unlike mutations, which are harder to reverse, if you stop smoking at a certain time and duration, then you have a chance to decrease your mathematics that might be due to the buildup of epigenetic changes.”

Baylin and his team are now looking into developing new treatment therapies which target the epigenetic abnormalities occurring in the lungs of smokers.

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About the Author

Linda Quan
Linda is a physics and chemistry graduate who loves to write in her spare time. She is also addicted to coffee and online shopping. On cold, moonless nights, she often ventures out with her camera to take pictures of the stars. You can find her on Instagram @duoettria.


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