January 07, 2019
3 min read

High-frequency basal cell carcinoma may signal increased risk for other cancers

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Kavita Sarin, MD, PhD
Kavita Sarin

Patients with frequent cases of basal cell carcinoma appeared to be at three times greater risk for developing other unrelated cancers, including blood, breast, colon and prostate cancers, according to study findings.

“We are hopeful that this finding could be one way to identify people at an increased risk for a life-threatening malignancy before those cancers develop,” Kavita Sarin, MD, PhD, dermatologist and assistant professor of dermatology at Stanford University Medical Center, said in a press release.

Investigators sought to assess whether 61 patients (mean age, 68.9 years; 75.4% men; 96.7% European descent; 85.2% Fitzpatrick skin type 2) receiving treatment at Stanford Health Care for frequent cases of basal cell carcinoma harbored germline mutations in 29 DNA repair genes. Researchers additionally investigated the association of frequent basal cell carcinoma with other cancer risks using the Truven MarketScan national insurance claims database.

The number of confirmed basal cell carcinoma cases per patient in the Stanford cohort over the 10-year observation period ranged from six to 65, with an average of 11 per patient.

Results of the single-institution pilot study showed nearly 20% of patients with high-frequency basal cell carcinoma harbored 13 pathogenic mutations in 12 genes, including APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN and PALB2.

Researchers observed a 3.2-fold increased risk for other malignancies among patients with frequent basal cell carcinoma in the Truven database and a 3.5-fold increased risk among patients in the Stanford cohort.

HemOnc Today spoke with Sarin about the study, potential explanations for the findings, and further research to learn more about these associations.

Question: How did the idea for this study come about?

Answer: In our dermatology clinics, we noticed that patients with similar sun exposure histories, skin pigmentation and lifestyles can develop very different numbers of skin cancers. This led us to suspect that an individual’s underlying genetics may play a significant role in contributing to the development of frequent skin cancers.

Q: How did you conduct the study?

A: We used medical records to identify the top 5% of patients who developed basal cell carcinoma treated at Stanford between 2005 and 2015. Patients were screened to ensure that they did not meet clinical criteria of genetic syndromes already known to increase the risk for basal cell carcinoma. We then asked these patients if they would be interested in participating in a study assessing the genetics of developing basal cell carcinoma.

Q: Can you summarize your findings?

A: We found that 19% of patients harbored a pathogenic mutation in a DNA repair gene, which was higher than we anticipated. Another surprising finding was that mutations occurred in well-known DNA repair genes, including BRCA genes and genes known to cause Lynch syndrome. When we examined our cohort, we found that these individuals were at increased risk for developing other malignancies. In a subset analysis, we analyzed a large national claims data set and found that individuals who developed six or more basal cell carcinomas had a similar increase in malignancy risk.


Q: What are the potential explanations for this finding?

A: There are a number of people walking around with inherited susceptibility to cancer. Unfortunately, many of these individuals are identified after they have developed a life-threatening malignancy. The skin is a great system to uncover these underlying DNA repair defects, likely because the skin is constantly subjected to mutagenesis from ultraviolet light. Our data suggest that the skin itself can serve as a biomarker for a potential underlying DNA repair defect.

Q: What are the clinical implications of these associations?

A: This is a single-institution pilot study, so while the results are striking, I would caution about generalizing the findings until results are replicated in other cohorts. Physicians should be suspicious when they see patients with extreme numbers of skin cancers. Should they find a compelling personal or family history of other malignancies, the physician should consider referring the patient to cancer genetics for further screening.

Q: What other research is underway, planned or necessary to learn more about these associations?

A: We are currently enrolling a larger cohort of patients to study the presence of DNA repair mutations as well as other cancer susceptibility mutations in patients who develop frequent basal cell carcinomas. We are also looking at other types of skin cancers and are in the process of enrolling a cohort of patients who develop multiple melanomas for a similar study.

Q: Is there anything else that you would like to mention?

A: One in three Caucasians in the U.S. will develop basal cell carcinoma. It is very common, and our data do not suggest that these individuals are more likely to carry a genetic mutation in DNA repair. Our findings only pertain to patients who develop extreme numbers of skin cancer. – by Jennifer Southall


Cho HG, et al. JCI Insight. 2018;doi:10.1172/jci.insight.122744.

For more information:

Kavita Sarin, MD, PhD , can be reached at Stanford Health Care, 3240 Alpine Road, Portola Valley, CA 94028; email: ksarin@stanford.edu.

Disclosure: Sarin reports no relevant financial disclosures.