The Sol Goldman Pancreatic Cancer Research Center


1% OF ASHKENAZI JEWS CARRY A DEFECTIVE COPY OF THE SECOND BREAST CANCER GENE AND ARE AT INCREASED RISK FOR DEVELOPING CANCER

Since the discovery of the second breast cancer gene, called BRCA2, in December of 1995, researchers have come to a better understanding of the role of BRCA2 in the development of cancer. Every cell in our body has two copies of BRCA2. One is inherited from our mother and one from our father. It turns out that an ancestor of Eastern European Jews, approximately 29 generations or 3000 years ago, developed a defect in the DNA coding for the BRCA2 gene. This DNA defect, known as the 6174delT mutation, has been passed from generation to generation. As a result, 1% of all Ashkenazi Jews living now inherit a defective copy of one of their BRCA2 genes. Unbeknownst to them, these carriers of the BRCA2 mutation are at increased risk for developing breast, ovarian and pancreatic cancer.

The risk of cancer to Jews who inherit a defective copy of BRCA2 varies in different families. The reason for this variation in risk is thought to be dependent on "lifestyle factors" such as smoking, dietary influences, the inheritance of other cancer susceptibility genes, and a certain element of chance. In addition, because the risk of cancer in a BRCA2 carrier continues throughout life, we will see more cancers caused by inherited BRCA2 mutations as our population ages.

While most attention in the media has been given to the risk of breast and ovarian cancer, carriers of the BRCA2 mutation are also at an increased risk of developing pancreas cancer. Current evidence suggests that in Jewish individuals who develop pancreatic cancer approximately 1 in 10 such cancers are caused by inherited BRCA2 mutations. Put another way, carriers of BRCA2 mutations have a 1 in ten to 1 in 20 chance of developing pancreatic cancer. Indeed, it was a critical discovery by scientists at The Johns Hopkins Hospital of a unique genetic alteration in a pancreatic cancer that led to the discovery of this gene.

Pancreatic cancer is the most lethal of all the cancers that BRCA2 carriers are at risk of developing. Unless pancreatic cancer is identified at a very early stage, this cancer is incurable and patients rarely live beyond two years. For those who are fortunate enough to be identified at an early stage, up to 40% of patients can be cured in specialist centers. Simply put, early detection is the key to winning the battle against pancreatic cancer.

One striking feature of carriers of mutations of the BRCA2 gene is that they may not suspect that they are carriers because they may not have a family history of cancer, despite the fact that their ancestors on one side of their family must also have carried the same mutation. There are many reasons for this subtlety. Not every individual with a BRCA2 mutation will develop cancer. As mentioned above other genetic and environmental factors influence the risk of developing cancer. A small family size or early death from other causes may also obscure a familial cancer predisposition. In addition, males with BRCA2 mutations may have a lower risk of developing cancer and they may therefore obscure a familial cancer predisposition. Clearly, the absence of a family history of cancer does not mean that one does not carry the BRCA2 mutation.

Scientists have now developed a clinical test for the BRCA2 mutation, but although this test is available, it may not be right for everyone. In deciding whether or not you want to have a gene test performed, you should speak with a trained genetic counselor so that you are fully informed of the issues at stake. Genetic counseling includes both pre-test and post-test counseling, and can be given by specialist genetic counselors or by physicians experienced in this area. Genetic counseling is important before one embarks on gene testing because although gene testing raises concerns about insurance liability and employer discrimination, knowledge of one's risk can empower an individual. A negative result can provide reassurance, while positive result may save a life through the early detection of cancer or possibly even with preventative surgery.

To schedule an appointment for genetic counseling, please contact The Johns Hopkins Clinical Cancer Genetics and Prevention Program at (410) 502-7082. A directory of genetic counselors in other areas may be found through the National Society of Genetic Counselors (NSGC) at http://www.nsgc.org.