Cancers, in general, are caused by a mixture of environmental and genetic factors. Skin cancer is also a mixture of the two, but the environment truly plays a greater role. In researching the lesser part, genetics, the results were sketchy. The genetics behind skin cancer depend on who you ask and when researching this subject we found case studies and papers that openly contradicted each other. The problem is that scientists aren't sure what's right. The papers located at The OMIM institute, were especially useful, up to date, and the basis for this section of our web page.
Skin cells are constantly being bombarded with radiation and certain genes are responsible for repairing the damage. A gene called "patched" was recently found that when inactivated caused an increase in excessive cell growth, also known as cancer. This gene was first found in the common fruit fly Drosophila melanogaster, a creature familiar to all genetics classes, and linked to the skin cancer Basal Cell Carcinoma. Located on the 9th chromosome in humans, its importance was discovered by two teams; one at Yale and the other at Stanford. It was found that malfunctioning patched led to many different kinds of skin cancer and even defective embryonic development. Patched is directly responsible for controlled cell death, which is called apoptosis. When this gene does not work tissue structure is not maintained, embryo's toes and fingers do not take shape, and skin cancer can grow unchecked.
Hedgehog, the gene that turns on the patched gene, can also lead to skin cancer when it does not function. The gene product of hedgehog is a protein that rests on the cell membrane and sends signals to the nucleus of the cell. The hedgehog protein determines cell growth among other things and activates several genes at the same time, including the gene patched. Patched proteins then build up in the cell and interrupt the signals being sent from the hedgehog protein. Put simply, hedgehog and patched want different things for the cell. Hedgehog wants cell growth, while as it activates genes to do this, it also activates patched. The built up patched blocks the signal and maintains the level of growth to a steady pace. This system of checks and balances is very fragile, but only if patched does not work will cancer ensue. If hedgehog had some mutation that rendered it useless, then patched would not be activated, the cell would not grow, and it would eventually die. Now if patched failed, then there would be nothing stopping the growth signal from hedgehog and a cancer cell would be born.
Another gene, p53, plays an important role in the cell cycle and when it does not function, cancers can form. Called p53 because the protein it codes has a molecular weight of 53,000 MU, it creates a transcription factor which regulates the cell cycle at the point when DNA is about to be replicated. When this transcription factor is working, the cell will find its DNA replication errors and either fix it or stop dividing if the damage is too great. When UV rays from the sun or another source hit the skin cells, point mutations often occur in many different genes. When the damaged cells reach the cell division stage in their life, the p53 gene is responsible for fixing these mutations or not letting the cell divide. If, though, the p53 gene was affected by the UV attack, then cell division would go unchecked and cancerous cells could result.
If one of the two genes, patched or p53, is inherited in a mutated way that affects its function, the chances for getting skin cancer is great. Those inheriting the mutated form of p53 have a 50% chance of chance of getting cancer by age 30 and a 90% chance by the time they are 70. Skin cancer in people who have the gene is very common, for skin cells are in a constant state of repair. When the cells cannot see their DNA damage, they will divide no matter what is wrong with them. Patched is usually born in a somatic cell so inheritance of a mutated version is rare. When it is inherited, the embryo usually cannot survive, since apoptosis is so important in embryo development.
These genes and their products work perfectly when not attacked from our environment, but there is no way to avoid this. The genetics behind skin cancer are still being discovered and this can only help in stopping the disease that we are in danger of getting every time we step outside.