A new genetic alteration that predisposes people to Cowden syndrome, a rare disorder that is characterized by high risks of breast, thyroid and other cancers has been identified by scientists.
Patients with Cowden syndrome and Cowden-like syndrome have mutations in the tumour suppressor PTEN gene.
These mutations are associated with increased risk of various malignancies, approximately 10 percent lifetime risk for thyroid cancer, and as much as 50 percent lifetime risk for female breast cancer over the general population, according to background information in the article.
Other mechanisms of loss of function could result in under expression of PTEN or of KILLIN, a novel tumour suppressor gene lying right next to PTEN, which may account for the remainder of Cowden syndrome and Cowden-like syndrome.
"In the context of a difficult-to-recognize syndrome, identification of additional cancer predisposition genes would facilitate molecular diagnosis, genotype-specific predictive testing of family members who are as yet clinically unaffected, genetic counselling, and medical management," the authors wrote.
They analyzed nucleic acids in 123 patients with Cowden syndrome or Cowden-like syndrome and 50 unaffected subjects without PTEN variants for germline methylation and expression of PTEN or KILLIN from August 2008 to June 2010.
They found that KILLIN was a predisposition gene for Cowden syndrome and Cowden-like syndrome.
"By discovering another cancer predisposition gene, we have added to the sensitivity of molecular diagnosis and predictive testing becomes possible. Importantly, genetic counseling and gene-informed risk assessment and management become evidence based," the researchers wrote.
"If our observations of 2- to 3-fold increased risks of renal and/or breast cancer with KILLIN germline methylation over those of PTEN mutation holds, then extra vigilance for the organs at risk, breast and kidneys, is warranted. The KILLIN-associated breast cancer risks would parallel those conferred by germline BRCAl/2 mutations," they added.
The preliminary research is published in the December 22/29 issue of the Journal of the American Medical Association.