The Process of Genetic Cancer Risk Assessment
What can I expect from my visit with a cancer risk counselor?
The process of cancer risk assessment begins with a detailed personal and family health history as well as a directed physical examination. Most patients have had clinicians ask them if they have a family history of cancer. Unfortunately, this approach automatically puts the patient in the position of determining what is and what is not significant regarding their family medical history. As a result, many individuals continue to have the misconception that a paternal family history of breast cancer for example, has no bearing on a woman's risk for breast cancer. The risk assessment process details family health information about both affected and unaffected relatives and documents all individuals within a family. Representation of the family history in pedigree format (Figure) enables recognition of potential inheritance patterns.
A discussion of any relevant hereditary syndromes and their associated risks should be individually tailored to the patient's current understanding, risk perception and personal and family medical history. The goal of the individualized risk assessment is to increase the patient's knowledge regarding cancer etiology (genetic and environmental) and to explain why his or her particular situation may require further investigation. Generally, this includes options for calculating cancer risk, strategies for cancer risk management, and a discussion surrounding the potential psychosocial implications of cancer risk assessment and testing. Hereditary predisposition testing can then be used in those with a significant probability of detection to confirm or disprove the presence of a specific mutation as the cause of the inherited risk.
What is a mutation?
A mutation is a change in the usual DNA sequence of a particular gene. Mutations can have a harmful, beneficial or a neutral effect upon health and can be inherited as traits that are dominant, recessive, or linked to a particular sex. Many of the mutations that predispose to cancer are dominant, meaning that it only takes one copy of the mutated gene to increase the risk of disease in an individual.
How is breast cancer risk inherited?
Inherited information is contained in every cell in our body on structures called chromosomes. Each individual has twenty-three pairs of chromosomes; one member of the pair comes from our father and one from our mother. Each chromosome contains thousands of genes. Like chromosomes we inherit two copies of every gene - one from our father and one from our mother. An alteration or mutation in one of these copies can be passed through generations and interfere with the proper functioning of the gene.
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The function of the BRCA genes is to maintain proper cell growth, division and repair of DNA damage. All individuals, regardless of whether or not they have cancer, have two copies of the BRCA genes. A mutation or alteration in one of these genes causes them not to function properly and increases the likelihood that cancer will develop. Each of these genes is inherited in an autosomal fashion and it only takes one altered breast cancer gene to cause the increased likelihood for cancer. If an individual has a parent with a non-working copy, he or she is at 50% risk for inheriting the working or the non-working copy. If he or she does not inherit the mutation, they are more likely to have the same risk of developing cancer as a person in the general population and they cannot pass any mutations to their children.
How is genetic testing performed?
Most often the test is performed from a simple blood sample. Rarely, cancer tissues can be used to determine if a mutation is present in a tumor sample.
Who might consider genetic cancer risk assessment?
There are many hereditary (genetic) factors that have been discovered which may significantly increase the risk of breast cancer and have implications for all aspects of medical management, including prevention, screening, and treatment. Genetic cancer risk assessment may be useful in women with breast cancer wanting to define the etiology of their breast cancer and understand their risk of a second primary tumor or to clarify risk to offspring. Some women may wish to consider genetic assessment when considering cancer treatment options. For those with a family history of disease, the process may aid in understanding their personal risk of breast cancer and define the appropriateness of particular surveillance approaches, or to aid in decision-making about risk-reducing prophylactic surgery. For those individuals who have a mutation in the family, testing may identify them as having a higher risk or provide a sense of reassurance that their risk is that of the general population.
Identifying a person with an increased risk of cancer can reduce the occurrence of cancer through clinical management strategies (e.g. tamoxifen for breast cancer or colonoscopy for colon cancer). Alternatively, genetic testing may improve an individual's quality of life through intrinsic benefits of knowing that there is no genetic predisposition to cancer.
Family characteristics that may suggest the presence of cancer predisposition include:
- Cancer in the family that is present in several generations.
- Transmission patterns suggesting that a gene mutation may have been passed through an individual that cannot or is less likely to develop the disease. For example, in the case of the hereditary breast and ovarian cancer syndrome, a male may inherit the risk of breast and ovarian cancer, but cannot develop ovarian cancer (because he does not have ovaries) and is less likely to develop breast cancer. Instead, he may pass the risk on to his sons and daughters, who may develop disease.
- Early age of onset of a cancer. Individuals who carry a mutation in a cancer predisposition gene typically develop disease at an earlier age than do those with sporadic disease.
- Two or more primary cancers occurring in the same individual. These could be multiple cancers of the same type (bilateral breast cancer) or primary cancers of different types (breast and ovarian cancer in the same individual).
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