Scientists have revealed multiple genetic discoveries that may permit easier diagnosis and disease management for Cowden syndrome patients who are predisposed to breast and kidney cancer.

The research, led by Charis Eng, Chair of the Genomic Medicine Institute at Cleveland Clinic, revealed KILLIN as a novel predisposition gene for Cowden syndrome (CS) and Cowden-like syndrome (CLS) features in individuals without germline PTEN mutations, which also plays a role in cancer risk.

Mutations in the PTEN gene are the foundation of Cowden syndrome. PTEN is a tumor suppressor gene, helping to direct the growth and division of cells.

Inherited mutations in the PTEN gene have been found in approximately 80 percent of Cowden syndrome patients. These mutations prevent the PTEN protein from effectively regulating cell survival and division, which can lead to the formation of tumors.

However, not all CS and CLS patients carry mutated PTEN. In fact, in CLS, less than 10 percent have PTEN mutations, yet they develop cancers just like CS.

In those patients without the PTEN mutation, 42 percent of Cowden syndrome patients and 33 percent of Cowden-like syndrome patients have low levels of KILLIN tumor suppressor gene.

"We know that 80 percent of Cowden patients carry the PTEN mutation and half of the remaining 20 percent carry the inactive KILLIN gene," Eng said.

"What that means is that altogether PTEN and KILLIN should account for 90 percent of all cases of classic Cowden syndrome, a huge step forward in diagnosing an often overlooked disease. More importantly, KILLIN and PTEN should account for almost half of CLS individuals."

This study shows that CS/CLS individuals with KILLIN promoter methylation, which switches the KILLIN gene off, have a threefold greater risk of breast cancer, and a twofold greater risk of kidney cancer, compared to those with mutant PTEN.

The study is published in the Dec. 22 issue of the Journal of the American Medical Association (JAMA).