Common
skin cancer can signal increased risk of other cancers
By KRISTA CONGER
People who develop
abnormally frequent cases of a skin cancer known as basal cell carcinoma appear
to be at significantly increased risk for the development of other cancers,
including blood, breast, colon and prostate cancers, according to a preliminary
study by researchers at the Stanford University School of Medicine.
The increased
susceptibility is likely caused by mutations in a panel of proteins responsible
for repairing DNA damage, the researchers found.
“We discovered that
people who develop six or more basal cell carcinomas during a 10-year period
are about three times more likely than the general population to develop other,
unrelated cancers,” said Kavita
Sarin, MD, PhD, assistant professor of dermatology.
“We’re hopeful that this finding could be a way to identify people at an increased risk for a life-threatening malignancy before those cancers develop.”
“We’re hopeful that this finding could be a way to identify people at an increased risk for a life-threatening malignancy before those cancers develop.”
Sarin is the senior
author of the study, which was published online Aug. 9 in JCI Insight.
Medical student Hyunje Cho is the lead author.
Largest organ
The skin is the
largest organ of the body and the most vulnerable to DNA damage caused by the
sun’s ultraviolet rays. Try as one might, it’s just not possible to completely
avoid sun exposure, which is why proteins that repair DNA damage are important
to prevent skin cancers like basal cell carcinoma.
Most of the time this system works well. But sometimes the repair team can’t keep up. Basal cell carcinomas are common — more than 3 million cases a year are diagnosed in the United States alone — and usually highly treatable.
Sarin and Cho wondered
whether the skin could serve as a kind of canary in the coal mine to reveal an
individual’s overall cancer susceptibility. “The skin is basically a walking
mutagenesis experiment,” Sarin said. “It’s the best organ to detect genetic
problems that could lead to cancers.”
Sarin and Cho studied
61 people treated at Stanford Health Care for unusually
frequent basal cell carcinomas — an average of 11 per patient over a 10-year
period. They investigated whether these people may have mutations in 29 genes
that code for DNA-damage-repair proteins.
“We found that about
20 percent of the people with frequent basal cell carcinomas have a mutation in
one of the genes responsible for repairing DNA damage, versus about 3 percent
of the general population. That’s shockingly high,” Sarin said.
Furthermore, 21 of the
61 people reported a history of additional cancers, including blood cancer,
melanoma, prostate cancer, breast cancer and colon cancer — a prevalence that
suggests the frequent basal cell carcinoma patients are three times more likely
than the general population to develop cancers.
‘A strong correlation’
To confirm the
findings, the researchers applied a similar analysis to a large medical
insurance claims database.
Over 13,000 people in the database had six or more basal cell carcinomas; these people also were over three times more likely to have developed other cancers, including colon, melanoma and blood cancers.
Finally, the researchers identified an upward trend: the more basal cell carcinomas an individual reported, the more likely that person was to have had other cancers as well.
Over 13,000 people in the database had six or more basal cell carcinomas; these people also were over three times more likely to have developed other cancers, including colon, melanoma and blood cancers.
Finally, the researchers identified an upward trend: the more basal cell carcinomas an individual reported, the more likely that person was to have had other cancers as well.
“I was surprised to
see such a strong correlation,” Sarin said. “But it’s also very gratifying. Now
we can ask patients with repeated basal cell carcinomas whether they have
family members with other types of cancers, and perhaps suggest that they
consider genetic testing and increased screening.”
The researchers are
continuing to enroll Stanford patients in the study, which is ongoing, to learn
whether particular mutations in genes responsible for repairing DNA damage are
linked to the development of specific malignancies.
They’d also like to conduct a similar study in patients with frequent melanomas. But they emphasized that there’s no reason for people with occasional basal cell carcinomas to worry.
They’d also like to conduct a similar study in patients with frequent melanomas. But they emphasized that there’s 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,”
Sarin said. “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.”
Other Stanford authors of the study are former dermatology resident Karen Kuo, MD; statistical programmer Shufeng Li; clinical research coordinator Irene Bailey; clinical professor of dermatology Sumaira Aasi, MD; associate professor of dermatology Anne Chang, MD; professor of dermatology Anthony Oro, MD, PhD; and professor of dermatology Jean Tang, MD, PhD.
The study was
supported by the Dermatology Foundation, the Stanford Society
of Physician Scholars, the American Skin Association and Pellepharm
Inc.
Tang and Epstein are
co-founders, directors and officers of Pellepharm, a biotechnology company
focused on rare dermatological conditions.
Stanford’s Department
of Dermatology also supported the work.
Krista Conger is a
science writer for the medical school's Office of Communication & Public
Affairs. Email her at kristac@stanford.edu.
