Genetic Cancers
Familial Adenomatous Polyposis (FAP)
Colorectal cancer is one of the most common malignant diseases. Many colorectal cancers originate from benign adenomas (tumors), as in the case of familial adenomatous polyposis (FAP), a genetic disease marked by numerous precancerous polyps in the colon and rectum.
These polyps usually develop in the second or third decade of a patient's life.
The likelihood that patients with FAP will develop colorectal cancer is almost 100 percent unless they undergo a prophylactic colectomy, which is a preventive procedure to remove all or part of the colon.
Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of hereditary colorectal cancer. It develops when people are relatively young and is indicated by polyps – but only a few, not hundreds as in familial adenomatous polyposis (FAP). Women with this condition also have a very high risk of developing cancer of the endometrium (lining of the upper part of the uterus). Other cancers associated with HNPCC include cancer of the ovary, stomach, small bowel, pancreas, kidney, ureters (tubes that carry urine from the kidneys to the bladder) and bile duct.
Physicians have found that families with HNPCC have certain characteristics:
- At least three relatives have colorectal cancer
- Two successive generations are involved
- At least one relative had their cancer when they were younger than age 50
- At least two of the people are first-degree relatives
These are called the Amsterdam criteria. If any of these hold true for your family, then you might want to seek genetic counseling. But even if your family history satisfies the Amsterdam criteria, it doesn't mean you have HNPCC. Only about 60 percent of families who have the Amsterdam criteria have HNPCC. The other 40 percent do not; and although their colorectal cancer rate is higher than normal (about two times), it is not as high as that of people with HNPCC (about six times).
A second set of criteria for HNPCC, which has been recently revised, is called the Bethesda criteria. These are used to determine whether a person with colorectal cancer should have their cancer tested for genetic changes called microsatellite instability (MSI). These criteria include at least one of the following:
- The person is younger than 50 years
- The person has or had another cancer (endometrial, stomach, pancreas, ovary, kidney, ureters or bile duct) that is associated with HNPCC
- The person is younger than 60 years and the cancer has certain characteristics seen with MSI when viewed under the microscope
- A first-degree relative has been diagnosed with a non-colorectal cancer often seen in HNPCC carriers (endometrial, stomach, pancreas, ovary, kidney, ureters or bile duct) and is younger than 50 years
- The person has two or more second-degree relatives who had an HNPCC-related tumor at any age
MSI testing is the first step in laboratory testing to identify people with HNPCC. If a patient meets Bethesda criteria and has a tumor with MSI, more genetic testing will be needed to confirm that there is a mutation of one of the HNPCC genes. Still, the majority of people who meet the Bethesda criteria do not have HNPCC. On the other hand, about 2 percent of people with colorectal cancer who do not meet any of these criteria still have HNPCC when they are tested.
Physicians should also be suspicious of HNPCC if, instead of colorectal cancer, the family members have other cancers associated with this gene mutation. These are endometrial cancers, ovarian cancers, small bowel cancers or cancer of the lining of the kidney or the ureters. Still, one family member younger than age 50 must have been diagnosed with colorectal cancer before a diagnosis of HNPCC is considered.
Accurate identification of families with these inherited syndromes is important. Then, physicians can recommend specific measures, such as screening and other preventive measures, at an early age. Because several types of cancer can be associated with inherited colorectal cancer syndromes, all people should check their family medical history for polyps or any type of cancer. Those who develop polyps or cancer should inform other family members. People with a family history of colorectal polyps or cancer should consider genetic counseling, to review their family medical tree and determine whether genetic testing may be right for them. This will help them to make decisions about getting screened and treated at an early age.
Hereditary Breast and Ovarian Cancer
BRCA1 or BRCA2 Mutation
The majority of breast and ovarian cancer cases are not hereditary. However, approximately 5 to 10 percent of all individuals with breast or ovarian cancer have inherited a mutation in a single gene which predisposes them to develop cancer. Two genes, BRCA1 and BRCA2 (Breast Cancer gene #1 and #2), appear to account for 90 percent of cases of hereditary breast and ovarian cancer. Both genes are thought to instruct the cell how to make proteins that eliminate errors in the DNA; these proteins are called tumor suppressors. When mutations occur in a tumor suppressor gene, the gene is rendered ineffective, and tumor development can result.
Individuals who inherit an altered copy of the BRCA1 or BRCA2 gene are born with only one working copy of the gene in every cell, including every breast cell. Therefore, all that is needed to cause cancer in a breast cell is for the "normal" gene to be damaged by environmental exposures. Individuals who inherit an altered copy of BRCA1 or BRCA2 often develop breast cancer at a younger age (on average, less than 45 years) because less time is needed for the one "normal" gene to be damaged.
If a woman inherits the altered BRCA1 or BRCA2 gene, there is up to an 85 percent chance that she will develop breast cancer at some point in her lifetime. There is also an up-to-65 percent risk of developing a second breast cancer, and a 15 to 40 percent lifetime risk of developing ovarian cancer.
Genetic testing for BRCA1 and BRCA2 is now available. Since both BRCA1 and BRCA2 are very large genes, it is very expensive and time-consuming to study both genes completely. If a family is considering testing, first test, if possible, a family member who has been diagnosed with cancer. If a mutation in either BRCA1 or BRCA2 exists in the family, it would most likely be identified in this individual.