Cleveland Clinic researchers have discovered that a gene is associated with Cowden syndrome, an inherited condition that carries high risks of thyroid, breast and other cancers, and a subset of non-inherited thyroid cancers.
Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy
Results appeared online today in American Journal of Human Genetics.
Cowden syndrome is a disorder characterized by noncancerous, tumor-like growths called hamartomas. These growths can appear on the skin, on mucous membranes and in the intestinal tract. At least one in 200,000 people are affected by the disease.
People with Cowden syndrome also have an increased risk of developing certain cancers – an 85 percent lifetime risk of breast cancer, a 35 percent risk for epithelial thyroid cancer, and increased risks of uterine, kidney and colon cancers as well.
Thyroid cancer is the second-fastest increasing cancer in women and fastest-increasing cancer in men during the last decade.
RELATED: Thyroid Cancer: Does It Run in the Family?
The gene’s link to Cowden syndrome was discovered by Charis Eng, MD, PhD, Founding Chair of Cleveland Clinic’s Genomic Medicine Institute and Director of the Center for Personalized Genetic Healthcare. The gene, whose name is SEC23B, encodes a protein involved in the transport of all proteins within cells.
Dr. Eng and her team started their gene-hunting journey three years ago by examining a multi-generational family with early-onset thyroid cancers. They found that all family members with thyroid cancer had inherited a harmful mutation in this gene. The mutation was not found in family members who did not have thyroid cancer.
“This isn’t the first time we discovered novel genetic mutations in Cowden syndrome,” Dr. Eng says. “What was truly remarkable is that the SEC23B gene had been identified back in 2009 as the cause of a very rare type of anemia, but not cancer.”
RELATED: Busting Myths About Your Genes and Breast Cancer
Hallmarks of cancer
With anemia, SEC23B function is lost. But Dr. Eng and her team discovered that normal thyroid cells with the mutated form of SEC23B grew faster, formed larger colonies, invaded more aggressively, and were able to survive in a very stressful microenvironment. These cell characteristics are all major hallmarks of cancer.
“Our data not only identified a novel cancer-predisposing gene, particularly in thyroid cancer, but also highlighted how cellular stress responses can be hijacked by cancer cells to promote their survival,” Dr. Eng says.
The research team’s further analyses uncovered that SEC23B mutations are present in up to 3 percent of unrelated Cowden syndrome patients and in 4 percent of patients with non-syndromic thyroid cancer.
Cowden syndrome remains an under-diagnosed and difficult-to-recognize condition, Dr. Eng says. Up to half of Cowden syndrome patients test negative for all known genetic mutations.
RELATED: Do Your Genes Increase Your Risk of Getting Cancer Twice?
Potential to help manage disease
“The discovery of this new cancer-predisposing gene will facilitate predictive genetic testing, risk assessment, genetic counseling and clinical management of Cowden syndrome,” Dr. Eng says.
Earlier, Dr. Eng discovered that Cowden syndrome is caused when a tumor suppressor gene called PTEN does not function properly. The gene has since been implicated in a number of other conditions, including a rare form of autism.
Breast cancer treatment guide
Read more expert advice from Charis Eng, MD, PhD on her blog.