Do we know what causes basal and squamous cell skin cancers?

Most basal cell and squamous cell skin cancers are caused by skin exposure to ultraviolet (UV) rays from sunlight, as well as from man-made sources such as tanning beds.

Repeated and unprotected sun exposure over many years increases a person’s risk of skin cancer. Most skin cancers are probably caused by exposures that happened many years earlier. The pattern of exposure may also be important. For example, frequent sunburns in childhood may increase the risk for basal cell cancer many years or even decades later.

DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects more than just how we look.

Some genes contain instructions for controlling when our cells grow, divide into new cells, and die. Genes that help cells grow and divide are called oncogenes. Genes that keep cell growth in check by slowing down cell division or causing cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. Changes in several different genes are usually needed for a cell to become cancerous.

UV radiation can damage DNA. Sometimes this damage affects certain genes that control how and when cells grow and divide. Usually the cells can repair the damage, but in some cases this results in abnormal DNA, which may be the first step on the path to cancer.

Researchers don’t yet know all of the DNA changes that result in skin cancer, but they have found that many skin cancers have changes in tumor suppressor genes.

The gene most often found to be altered in squamous cell cancers is called TP53. This tumor suppressor gene normally causes cells with damaged DNA to die. When TP53 is altered, these abnormal cells may live longer and perhaps go on to become cancerous.

A gene often mutated in basal cell cancers is the “patched” (PTCH) gene, which is part of the hedgehog signaling pathway. This pathway is vital in the development of the embryo and fetus and is important in some adult cells. PTCH is a tumor suppressor gene that normally helps keep cell growth in check, so changes in this gene can allow cells to grow out of control. People who have basal cell nevus syndrome, which is often inherited from a parent and results in many basal cell cancers, have an altered PTCH gene in all the cells of their body.

These are not the only gene changes that play a role in the development of skin cancer. There are likely to be many others as well.

People with xeroderma pigmentosum (XP) have a high risk for skin cancer. XP is a rare, inherited condition resulting from a defect in an enzyme that repairs damage to DNA. Because people with XP are less able to repair DNA damage caused by sunlight, they develop huge numbers of cancers on sun-exposed areas of their skin.

The link between squamous cell skin cancer and infection with some types of the human papilloma virus (HPV) also involves DNA and genes. These viruses have genes that affect the growth-regulating proteins of infected skin cells. This can cause skin cells to grow too much and to not die when they're supposed to.

Scientists are studying other links between DNA changes and skin cancer. In the future, better understanding of how damaged DNA leads to skin cancer might be used to design treatments to overcome or repair that damage.