In the largest-to-date study of the most common form of skin cancer, basal cell carcinoma, researchers at Stanford University School of Medicine identified 31 genetic associations for the disease, 14 of which were identified for the first time.
Skin cancer is the most common type of cancer and there are three main types — basal cell carcinoma, squamous cell carcinoma, and melanoma, all named after the affected cell types. Basal cell carcinoma, the most common, affects more than four million people annually in the United States alone — and although it can be disfiguring it is rarely life-threatening. Squamous cell carcinoma affects more than one million people annually and leads to about nine thousand deaths each in year in the United States. Melanoma is extremely rare, but it is also deadly.
The new basal cell study follows another recent study by the same group at Stanford that focused on squamous cell carcinoma. Both studies were carried out in a similar two stage fashion. In collaboration with 23andMe, scientists first conducted a large genome-wide association study using 23andMe customers who consented to participate in research and had reported having either basal cell carcinoma or squamous cell carcinoma. Then, a confirmatory genome-wide association study was performed using data from a different cohort of research participants, either from the Nurses’ Health Study or the Health Professionals Follow-Up Study.
Roughly 17,000 cases and nearly 290,000 controls were included in the new basal cell study. The researchers confirmed 17 previously reported genetic associations and identified 14 novel susceptibility regions. Some of the genetic associations are with genes or gene regions thought to regulate skin cells. Other regions are involved in maintaining telomeres — the ends of chromosomes that either become too long or too short in many cancers — regulating the immune system, and tumor progression. The 31 genetic associations identified in this study are estimated to explain almost 11 percent of the familial relative risk for basal cell carcinoma.
Interestingly, many of the regions associated with basal cell carcinoma appeared to exert a bigger effect in younger individuals, which suggested that environmental factors for basal cell carcinoma might become more influential with age. When the scientists tested for interactions between the genetic markers and UV exposure, hair color, number of sunburns, and tanning ability, they found a significant interaction between a genetic marker in a gene called LPP and hair color, specifically light brown and dark brown/black hair groups. This finding suggests that the LPP marker is exerting a bigger effect on risk for basal cell carcinoma in people with brown or black hair.
Overall, the new basal cell carcinoma study expands our knowledge of the genetic factors that contribute to the most common form of skin cancer. Understanding what drives cancer, both the genetic and environmental factors, and the combination of the two, will ultimately help researchers predict who is at risk, make diagnoses quicker, and develop more precise treatments.
The study appeared in the journal Nature Communications.