Genetic Testing and Cancer
Cancer is caused by changes (mutations) in genes. As humans, we have 20,000 genes in each cell of our bodies. Genes are the recipes for how our bodies grow and develop. Some genes are involved in controlling cell growth and replication or in gene repair. When the gene has a mutation it cannot perform its usual function. Cells can start to grow out of control and become cancer cells, able to grow and spread to other parts of the body.
We can inherit gene mutations from our parents. These are called germline mutations and these mutations can be passed from generation to generation.
Our genes can also become damaged from exposures in our environment, such as air pollution or sun exposure, or just from the aging process. Lifestyle choices such as tobacco use can also damage our genes. Mutations that occur from environmental or lifestyle exposures are called acquired or sporadic mutations. Acquired mutations are not inherited from family members or passed to subsequent generations.
Recommendations about genetic testing for germline mutations are often based on personal or family history of disease. Genetic counselors can review these histories and evaluate for possible inherited risks of cancer.
There are several known inherited conditions that can lead to cancer. An inherited condition is one where the cancer risk is passed down in a family from generation to generation through mutations in the genes.
Hereditary Breast and Ovarian Cancer
Hereditary breast and ovarian cancer syndrome (HBOC) is a genetic condition that puts people at a higher risk for breast cancer and ovarian cancer. The two genes most commonly associated with HBOC are BRCA1 or BRCA2. The lifetime risks for breast cancer for those diagnosed with HBOC are estimated to be 50-85% and for ovarian cancer are 15-45%. The risks to develop a second primary breast cancer in the five years after an initial diagnosis range between 12-20%. Mutations in the BRCA1 and BRCA2 genes are also associated with increased risks of prostate cancer, pancreatic cancer, and melanoma. Identification of a BRCA1 or BRCA2 mutation in a family can help shape treatment and surgical decisions for patients with cancer and guide cancer surveillance recommendations for early detection and cancer prevention for at-risk family members.
Lynch syndrome is the most common hereditary cause of colorectal cancer, responsible for 2-4% of all colorectal cancers. This syndrome is caused by mutations in one of several genes: MLH1, MSH2, MSH6, PMS2 or EPCAM. Without adequate intervention, such as regular colonoscopies, and depending on the gene involved, individuals with Lynch syndrome have up to a 61% risk of colorectal cancer. Women with Lynch syndrome also have up to a 57% risk of endometrial cancer. There are also increased risks of ovarian cancer and a small increased risk for urinary tract, biliary, kidney, stomach, and small intestine cancer. Identification of a Lynch syndrome mutation in a family can help shape treatment and surgical decisions for patients with cancer and guide cancer surveillance recommendations for early detection and cancer prevention for at-risk family members.
Familial adenomatous polyposis
Mutations in the APC gene are responsible for familial adenomatous polyposis (FAP), which is characterized by a proliferation of adenomatous polyps, benign (noncancerous) growths throughout the colon and rectum that can eventually become cancerous. Carriers of APC mutations have a greater than 90% chance of colorectal cancer before age 50 unless a prophylactic colectomy (removal of the colon to prevent cancer) is performed. Individuals who carry an APC gene mutation also are at significant risk to develop cancers outside the colon after they have a prophylactic colectomy. The risk of cancer outside the colon in individuals with FAP is 11% by age 50 and 52% by age 75.
People who have fewer than 100 polyps due to their APC gene mutation may have a milder form of the condition, which is called Attenuated FAP syndrome (AFAP). People with AFAP have a lower risk for colorectal cancer than people with FAP, but the risk is still very high. Identification of an APC mutation in a family can help shape treatment and surgical decisions for patients with cancer and guide cancer surveillance recommendations for early detection and cancer prevention for at-risk family members.
Multiple Endocrine Neoplasia type1 (MEN1)
Multiple endocrine neoplasia type 1 (MEN1) syndrome is associated with tumors of the endocrine (hormone-producing) glands and parts of the small intestine and stomach. MEN1 is diagnosed by the presence of multiple endocrine tumors. The most common tumors with MEN1 are found in the parathyroid gland, pancreas, and the pituitary gland and cause these glands to release excessive hormones.
Hereditary diffuse gastric cancer
Mutations in the CDH1 gene cause hereditary diffuse gastric cancer (HDGC). People with CDH1 gene mutations have a 56 -70% percent chance of developing stomach (gastric) cancer in their lifetime. Women with these mutations also have a 40-50% chance of developing lobular breast cancer, or breast cancer that begins in the milk-producing glands (lobules) of the breast. Identifying a CDH1 mutation can shape treatment and surgical decisions and guide cancer surveillance recommendations for early detection and cancer prevention.
Hereditary pancreatic cancer
Approximately 15% of cases of pancreatic cancer can be attributed to an identifiable genetic syndrome. Germline mutations in BRCA1 and BRCA2, CDKN2A, STK11, ATM, PALB2 and the Lynch syndrome genes, for example, are associated with an increased risk for pancreatic cancer. There are also families in which several members have had pancreatic cancer but no genetic cause has been identified. Individuals with a genetic susceptibility to, or a strong family history of pancreatic cancer may be candidates for enhanced screening of the pancreas by endoscopic ultrasound or abdominal MRI/MRCP to aid in the early detection of pancreatic cancer
Von Hippel-Lindau syndrome
Von Hippel-Lindau (VHL) syndrome is a condition caused by mutations in the VHL gene. VHL syndrome is characterized by a tendency to form tumors called hemangioblastomas, which primarily occur in the brain, spinal cord and retina. There is also an increased risk for pheochromocytomas (a rare tumor that develops in an adrenal gland), renal cell carcinoma (a type of kidney cancer), and cysts in the kidney or pancreas. Some of these tumors, especially in the kidney or pancreas, can progress to cancer if not treated appropriately. Screening recommendations for individuals with a confirmed diagnosis of VHL include annual blood pressure monitoring, annual imaging of the abdomen, annual eye exams, annual lab tests, and periodic imaging of the central nervous system. In 80% of cases, VHL syndrome is inherited from a parent, however, in 20 % of cases, a person may have VHL syndrome as a result of a new (de novo) mutation. Genetic testing for VHL syndrome is extremely sensitive and can typically determine whether or not additional screening is needed. New-York Presbyterian/Columbia University Irving Medical Center is proud to be recognized by the Von Hippel-Lindau Alliance as a Comprehensive Clinical Care Center.