Second Gene Linked to Familial Testicular Cancer
Specific variations or mutations in a particular can gene raise a man's risk of familial, or inherited, testicular germ-cell cancer, the most common form of this disease. This is only the second gene to be identified that affects the risk of familial testicular cancer, and the first gene in a key biochemical pathway.
Balintfy: Researchers have suspected for years that heredity plays a role in some patients with testicular germ-cell cancer, the most common form of the disease. Now a recent study shows that multiple genes with weaker individual effects—but acting together—probably influence an individual's risk of familial testicular cancer.
Stratakis: It appears that this particular tumor, like many other tumors in young adults, has a strong genetic component.
Balintfy: Dr. Constantine Stratakis is with the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Stratakis: Investigators believe that there is a lot of genetic factors that play a role together in increasing somebody's risk for developing testicular cancer.
Balintfy: Men with a family member who had a testicular germ cell cancer have greater risk than other men of developing testicular cancer. Although a family history probably accounts for less than five percent of all testicular cancers, the careful study of rare familial cancer clusters has often led to important new understanding of the non-familial versions of the same cancer.
Stratakis: So the key finding here is that we found inactivating mutations in a gene that regulates cyclic AMP levels. Cyclic AMP is a Cyclic nucleotide that is involved in signaling. It mediates the affects of many of the hormones that regulate testicular function.
Balintfy: Dr. Stratakis says Cyclic AMP is one of the most ancient signaling pathways that regulates how cells respond to hormones. It regulates practically everything from cell growth and proliferation to cell metabolism and function.
Stratakis: The role of Cyclic AMP signaling in testicular function and growth has been known for years. But this is the first time that mutations in a gene that regulate the Cyclic AMP levels were linked to a risk for a tumor.
Balintfy: The researchers found that seven different mutations in a specific gene, created abnormal versions of an enzyme that slowed down the enzyme's destruction of cyclic AMP. But Dr. Stratakis adds, the mutations don't cause cancer directly, but instead appear to increase an individual's susceptibility to developing a tumor.
Stratakis: It has been said that we all carry anywhere from 7 to 10 mutations in important genes; we don't necessarily have disease as a result of these mutations, but we are carriers of mutations of potentially giving us disease.
Balintfy: To conduct the research for this study, Stratakis and his colleagues analyzed the portion of the DNA from 95 familial testicular cancer patients that contains the gene PDE11A. He says learning how disruptions in the PDE11A enzyme lead to an increased risk of tumor formation may help researchers identify other proteins that also play a role. This is Joe Balintfy, National Institutes of Health, Bethesda, Maryland.