Today, I am going to focus on lung cancer. Why? Because it is the third, just after breast and prostate, most common cancer world-wide. Only in The UK, it accounts for 13% of all cancer cases. If we take into consideration, that there is more than 200 different types of cancers – lung cancer incidence looks quite impressive. (1)
For these who just got out of a cave: what is cancer? It is an uncontrolled multiplication of our mutated (immortal) cells, which grows into so-called tumour. It invades the organism by destroying its surrounding tissue. Cancerous cells may spread to other organs of our body through the bloodstream or lymphatic system.
As it is with any cancer, there are multiple reasons and causes of lung cancer. Nevertheless, I am going to focus on what happens on the molecular level, since the mechanism is pretty much the same in all cases.
The cells creating our body are not that easy to be invaded by cancer. There are some quite clever mechanisms to stop the cell grow or force it to commit suicide when it starts freaking out and getting out of control. The main guy inside our cells which is a sort of anti-cancer policeman [scientifically speaking, a t u m o u r r e p r e s s o r ] is a protein p53. Its name literally means that this is a protein 53kDa in size. In ’80, scientists used to estimate protein sizes on polyacrylamide SDS gels during electrophoresis. They would compare locations of the bands on a gel against a standard molecule. Nowadays, they use mass spectrometry, which allows to sum up the masses of all the amino acids making up a particular protein with a very high resolution. The updated size of our beloved P53 is actually only 43.7kDa, but nobody even thought about changing its name.
P53 is produced in our cells all the time and it can quickly trigger a response to a DNA damage or other growth abnormalities. P53 has a good sense of what is going on inside the cell. That cellular policeman has also quite a lot of power – it can kill the cell anytime or make it stop growing until the DNA is fixed. That’s why p53 needs someone who will keep an eye on it, so it doesn’t kill the cell by mistake or because it had a bad day. Its best friend is called Mdm2 and it binds p53 for most of the time, allowing cell to grow and proliferate. When DNA damage or some sort of abnormality happens within the cell, the stress activates a special type of genes which produce many phosphorylating molecules. These molecules tag p53 by attaching phosphate groups to its tail. It forces Mdm2 to release its friend free, allowing p53 to orchestrate a temporary arrest or cell death [ a p o p t o s i s ].
So we know what happens in a healthy cell. Now let’s see what happens in a cancerous lung cell.
In the cell which becomes cancerous, the protein p53 is not functional. It does not protect our healthy cells neither instruct the mutated ones.
Why is it not functional? Because the gene which encodes for p53 is being mutated.
How does it happen?
For example, when a Group 1 carcinogen (by IARC (2) ) – Benzo(a)pyrene (BaP) binds to our DNA. This molecule likes some parts of DNA more than others and in case of the lung cancer, it is attracted to a position [c o d o n] 157. It muddles up this region of the gene making one of the base pairs (Guanine, G) to be replaced by Thymine (T). This G to T replacement causes p53 to not function as it should. (3)
What is the effect of this mutation?
If the cell is put under a stress, the signalling molecules do not alert p53. A lack of functional p53 leads to cell dividing faster than others becomes immortal. This is when cancer starts.
Is BaP only in cigarettes tar?
Unfortunately not. In cigarettes tar the concentration of BaP reaches about 42ng/g (48ng/g in cigars). There is also a significant amount of BaP in air pollution (average concentrations in Europe visible on a map below). Of course smokers are far more prevalent to get a lung cancers than non-smokres, but air statistics show us that nobody is protected from those nasty substances.
There is a reason why lung cancer is so common world-wide. The amount of people smoking cigarettes between 1950 and now has dropped dramatically, nevertheless we all breath the same air every single day.
Remember, BaP is not the only nasty substance causing cancer and lung cancer is not the only one caused by BaPs!
I hope you enjoyed some molecular insights of lung cancer. Without calling you to stop smoking right now or showing you any nasty pictures of black lungs… I would simply like to make you more aware of the world surrounding us.