Individuals who develop frequent basal cell carcinomas may have an increased prevalence of germline mutations in DNA repair genes and an increased malignancy risk.
Individuals who develop frequent basal cell carcinomas (BCCs) may have an increased prevalence of germline mutations in DNA repair genes as well as an increased malignancy risk, according to researchers at Stanford University. Their report, published in JCI Insight, suggests that frequent BCCs may be external markers of inherited cancer risk.
“Our study found that upwards of 20% of individuals who developed frequent basal cell cancer had a gremlins defect in a DNA repair gene. While we hypothesized that DNA repair mutations contribute to increased cancer susceptibility, we were surprised at how high the prevalence of DNA repair mutations was in this cohort,” said study investigator Kavita Sarin, MD, PhD, an assistant professor of dermatology at Stanford University School of Medicine in Redwood City, California.
Sarin and colleagues followed 61 patients with unusually frequent BCCs who underwent germline analysis of 29 DNA repair genes between January 2005 and December 2015. They also conducted a case-control, retrospective review to examine the association of malignancies with frequent BCCs in a large US medical insurance claims database, Truven. The database included 13,264 individuals with 6 or more BCCs, all of whom were seen between 2007 and 2011.
The researchers found that 19.7% of patients in the frequent BCCs cohort harbored pathogenic mutations in the following DNA repair genes: APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. In addition, individuals with 6 or more BCCs had an increased risk of other malignancies. Overall, the risk for other malignancies increased by 3.5-fold in the frequent BCC cohort and by 3.2-fold in individuals included in the database.
“We are expanding our cohort. We are investigating other mutations and clinical risk factors that contribute to the increased basal cell cancer seen in patients, particularly in the 80% of patients who did not have identified DNA repair mutations,” Sarin told Cancer Network.
Stephanie Savory, MD, an assistant professor of dermatology at UT Southwestern Medical Center in Dallas, said this is an interesting and novel study. “We have long known that the skin provides a ‘window’ into overall systemic health. Many internal diseases have an early manifestation on the skin. It would be very useful if the skin could also give us an indication of future cancer risk,” Savory told Cancer Network.
A host of unavoidable and highly individualized confounders contribute to the development of non-melanoma skin cancer such as BCC, Savory added. Risk factors, such as skin type, genetic predisposition to photodamage, history of cigarette smoking, history of indoor tanning, and outdoor activities, can influence skin cancer risk, she explained. “However, this study suggests that development of multiple non-melanoma skin cancers, specifically BCC, reflects a systemic genetic deficiency or aberration in certain genes responsible for DNA repair. The implications are huge,” said Savory.