High Frequency of Common Skin Cancer May Warrant More Intensive Cancer Screening

Individuals who develop six or more basal cell carcinomas — a common type of skin cancer – during a 10-year period may be at three times the risk for developing another, unrelated cancer, according to preliminary study results published in JCI Insight.

The researchers, from Stanford University School of Medicine, noted the increased susceptibility for these unrelated cancers — including blood, breast, colon and prostate cancers – may be caused by mutations in a panel of proteins responsible for repairing DNA damage.

However, of note, they emphasized that there is no reason for people with occasional basal cell carcinomas to worry.

“About 1 in 3 Caucasians will develop basal cell carcinoma at some point in their lifetime,” senior author Kavita Sarin, M.D., Ph.D., assistant professor of dermatology at Stanford University School of Medicine, said in a press release.

“That doesn’t mean that you have an increased risk of other cancers. If, however, you’ve been diagnosed with several basal cell carcinomas within a few years, you may want to speak with your doctor about whether you should undergo increased or more intensive cancer screening.”

DNA repair in basal cell carcinoma comes in to play when the proteins that are important to prevent skin cancers like basal cell carcinoma are damaged from the sun’s ultra violet rays. When this DNA repair mechanism fails, individuals may be at an increased risk to develop skin cancers.

“Basal cell carcinoma is a relatively benign skin cancer caused by UV exposure, which develops in over 3 million people in the US annually. We hypothesized that the constant barrage of UV-induced mutagenesis in the skin may uncover early deficiencies in DNA repair and, accordingly, that frequent basal cell carcinoma could be a clinical marker of underlying defects in DNA repair,” the researchers wrote.

Therefore, they enrolled 61 patients with unusually frequent basal cell carcinomas — an average of 11 per patient over a 10-year period – to investigate whether these individuals possessed mutations in 29 genes that code for DNA-damage-repair proteins. To verify the association between basal cell carcinomas and other unrelated cancer risks, the researchers used a large national insurance database to conduct a parallel, case-control retrospective review, which included over 13,000 individuals with six or more basal cell carcinomas.

A total of 12 patients with high-frequency basal cell carcinoma (9.7 percent) harbored 13 of the reported pathogenic mutations in 12 genes, including APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN and PALB2.

Overall, 21 patients (34.4 percent) reported having a personal history of additional cancers — including invasive melanoma (five patients), blood cancer (five patients), prostate cancer (five patients), breast cancer (two patients) and colon cancer (two patients) – a prevalence that suggests that patients with frequent basal cell carcinoma are three times more likely than the general population to develop cancers, according to a Stanford Medicine press release.

“Increased frequency of mutations in the DNA repair pathways may reflect the greater susceptibility of these individuals to the environmental contribution of UV damage,” the researchers wrote. They added that earlier onset of first skin cancer may also suggest a higher contribution from genetic susceptibility.

Individuals with six or more basal cell carcinomas demonstrated an increased risk of other malignancies, with a 3.5-fold increase among the cohort of 61 patients, and a 3.2-fold increase among those in the large national insurance database.

In particular, individuals with high-frequency basal cell carcinoma appeared to be at an increased risk for leukemia and lymphoma (3.5-fold risk), colon cancer (4.5-fold risk), breast cancer (5.6-fold risk) and prostate cancer (4.7-fold risk).

Lastly, the researchers identified an upward trend among those who developed more basal cell carcinomas: The more they reported, the more likely the individual was to have had other cancers.

“Given the overall (ordinary) nature of basal cell carcinoma and the earlier onset of disease compared with internal malignancies, frequent basal cell carcinomas may serve as a low-risk clinical marker to identify a subset of individuals at highest risk of internal malignancies,” the researchers concluded. “These patients may benefit from clinical screening for family history of malignancy and multigene cancer-susceptibility panel testing.”

The researchers are continuing to enroll patients in to the study, which is ongoing, to determine whether particular genetic mutations are responsible for repairing DNA damage, which in turn, would be linked to the development of specific cancer types.

“A better understanding of how multigene panel testing can be incorporated in clinical care is warranted before a widespread implementation,” they added. “In addition, a further characterization of gene-environment interaction in patients with frequent basal cell carcinomas is needed to identify risk factors that may be independently associated with increased malignancy.”