Cancer occurs when the normal mechanisms that control cell growth are not working properly, either due to acquired or inherited mutations. Acquired mutations can be caused by a variety of environmental factors, such UV exposure, radiation, chemicals, or random events.
Hereditary cancers account for 5-10% of all cancers. They result from inherited cancer-causing mutations in genes passed down generation to generation which, when combined with acquired mutations, significantly increase an individual’s risk to develop cancer above the rate of the general population. For sporadic cancer, the individual’s cells have acquired mutations that disrupt the normal function of one or more genes, causing the cells to grow out of control. These mutations happen randomly and are not passed through the families. These individuals do not have inherited cancer-causing mutations.
Approximately 5-10% of breast cancer and 15% of ovarian cancer is hereditary. The vast majority of these hereditary cancers are caused by mutations in the BRCA1 and BRCA2 genes. Approximately 1 in 40 individuals of Ashkenazi Jewish descent is a carrier for a BRCA mutation, leaving these individuals at a higher risk of developing breast and ovarian cancer. This is compared to mutation frequency of 1 in 500 in the general population. These mutations are inherited in an autosomal dominant pattern, so males and females with such a mutation, whether they develop cancer or not, have a 50% chance of passing on the gene mutation to the next generation. In order for a person who inherits an abnormal BRCA gene from one parent to develop cancer, a second acquired mutation in the other, normal BRCA gene acquired from the other parent, must occur.
Approximately 10% of colorectal cancer (CRC) is hereditary. A significant portion of hereditary CRC is due to two known genetic syndromes: Familial Adenomatous Polyposis (FAP) and Lynch syndrome (Hereditary Non-Polyposis Colon Cancer - HNPCC). The mutations associated with these syndromes are inherited in an autosomal dominant pattern, so affected individuals have a 50% chance of passing on the gene mutation to the next generation. The likelihood of an Ashkenazi Jew having FAP or Lynch Syndrome is not increased compared to non-Jewish individuals, but those who have Lynch syndrome may have a specific mutation seen in particularly Ashkenazim.
There are many other cancer syndromes caused by inherited mutations. In general they are not increased in Jewish people compared to the general population.
Hereditary Diffuse Gastric Cancer/ Lobular Breast Cancer: Caused by mutation in the CDH1 gene associated with stomach, breast and colon cancer
Li Fraumeni Syndrome: hereditary mutation of the p53 gene associated with sarcomas, brain tumors, leukemia, adrenal and breast cancers.
Cowden’s Syndrome: hereditary mutation of the PTEN gene associated with breast cancer, thyroid (follicular) cancer and endometrial cancer
Von Hippel Lindau Syndrome: hereditary mutation of VHL gene associated with an increased risk of kidney cancer and benign blood vessel tumors
Multiple Endocrine Neoplasm Syndrome: associated with increased risk of tumors of the endocrine organs (pancreas, thyroid, pituitary, adrenal) which can be benign or malignant.
Genetic testing may not be right for everyone, but it can be helpful for you and your doctor to know about the increased health risks so that together you can determine a management plan that is right for you. This may include more frequent examinations, blood tests, and/or imaging, or risk-reducing surgeries. Some people choose not to undergo genetic tests but proceed with increased cancer surveillance as if they are at high risk.
Still curious about hereditary cancer?
Feel free to contact the Center, our on-staff genetic counselor can work with you to answer your questions or to refer you to the appropriate organization or a genetic counselor in your area.