A new study has suggested that a person’s risk of developing skin cancer is likely caused by genetics, as well as sun exposure. The work led by researchers at the Cleveland Clinic and medical genetics company Invitae is due to be presented at the American Society of Clinical Oncology (ASCO) conference in Chicago this week.
The study involved 400 people with melanoma and used commercial genetic testing to look for variants in 85 genes associated with cancer. Melanoma, the most serious form of skin cancer can be particularly dangerous if it is not diagnosed early as it can spread to other parts of the body, making it much harder to treat. Sun exposure is often perceived to be the main risk factor for developing melanoma, but the new study showed that 15.3% of people with melanoma have pre existing variants in genes which are known to correlate with an increased risk of developing cancer.
“Previously, it was thought that few melanoma patients would demonstrate a pathogenic germline variant in cancer susceptibility genes indicating an inherited component to their melanoma risk,” said Joshua Arbesman, MD, dermatologist at Cleveland Clinic and senior author of the study.
Hereditary genetic variants are generally passed down through generations of people and variants in specific genes are associated with different types of cancers. For example, mutations in the BRCA genes are associated with the development of early onset breast cancer and ovarian cancer, but can also increase the risk of melanoma too. Harmful variants in genes controlling a genetic repair process called DNA mismatch repair are commonly associated with a condition called Lynch Syndrome, where carriers are at increased risk of developing several types of cancer including colorectal cancers, at earlier ages than would be expected than people in the general population.
In the new melanoma study, 32.7% of the genetic variants found were known to be associated with an increased risk of melanoma. The remaining two-thirds of variants found were known to be correlated with an increased risk of developing cancers, but not specifically melanoma.
One important point to take into account when interpreting the study findings is that the researchers did select melanoma patients who had a personal or family history of multiple cancers, increasing the chance of genetic variants being found in these people, compared to in the general population. In a publicly available dataset of 470 melanoma patients which had not been selected based on family history or multiple cancers, 10.6% of patients had a genetic variant which likely increased their cancer risk, compared to 15.3% in the study. Two more datasets of melanoma patients with selection of patients showed between 14.5-15.8% of the individuals to have genetic variants likely predisposing to cancer development.
“Our results suggest that about 1 in 6 melanoma patients would have an inherited variant in cancer genes,” said Arbesman. “This means that these particular patients would benefit from cancer specific screening (separate from skin screening) that could catch other cancers earlier. We found similar results using multiple datasets with variable inclusion criteria, suggesting this may be potentially applicable to many melanoma patients, “he added.