Genetic Cancer Predisposition

What is a genetic cancer predisposition?

The etiology of cancer is multifactorial, with genetic, environmental, medical, and lifestyle factors interacting to produce a given malignancy. Knowledge of cancer genetics is rapidly improving our understanding of cancer biology, helping to identify at-risk individuals, furthering the ability to characterize malignancies, establishing treatment tailored to the molecular fingerprint of the disease, and leading to the development of new therapeutic modalities. As a consequence, this expanding knowledge base has implications for all aspects of cancer management, including prevention, screening, and treatment.

Genetic information provides a means to identify people who have an increased risk of cancer. Sources of genetic information include biologic samples of DNA, information derived from a person’s family history of disease, findings from physical examinations, and medical records. DNA-based information can be gathered, stored, and analyzed at any time during an individual’s life span, from before conception to after death. Family history may identify people with a modest to moderately increased risk of cancer or may serve as the first step in the identification of an inherited cancer predisposition that confers a very high lifetime risk of cancer. For an increasing number of diseases, DNA-based testing can be used to identify a specific mutation as the cause of inherited risk and to determine whether family members have inherited the disease-related mutation.

Throughout this summary, the term “mutation” will be used to refer to a change in the usual DNA sequence of a particular gene. Mutations can have harmful, beneficial, neutral, or uncertain effects on health and may be inherited as autosomal dominant, autosomal recessive, or X-linked traits. Mutations that cause serious disability early in life are usually rare because of their adverse effect on life expectancy and reproduction. However, if the mutation is autosomal recessive—that is, if the health effect of the mutation is caused only when two copies (one from each parent) of the mutated gene are inherited—mutation carriers (healthy people carrying one copy of the altered gene) may be relatively common in the general population.

"Common" in this context refers, by convention, to a prevalence of 1% or more. Mutations that cause health effects in middle and older age, including several mutations known to cause a predisposition to cancer, may also be relatively common. Many cancer-predisposing traits are inherited in an autosomal dominant fashion, that is, the cancer susceptibility occurs when only one copy of the altered gene is inherited.

For autosomal dominant conditions, the term “carrier” is often used in a less formal manner to denote people who have inherited the genetic predisposition conferred by the mutation.

Increasingly, the public is turning to the Internet for information related both to familial and genetic susceptibility to cancer and to genetic risk assessment and testing. Direct-to-consumer marketing of genetic testing for hereditary breast and colon cancer is also taking place in some communities. This wider availability of information related to inherited cancer risk may raise concerns among persons previously unaware of the implications inherent in their family histories and may lead some of these individuals to consult their primary care physicians for management advice and recommendations. In many instances, the evaluation and advice will be relatively straightforward for physicians with a basic knowledge of familial cancer. In a subset of patients, the evaluation may be more complex, calling for referral to genetics professionals for further evaluation and counseling.

Correctly recognizing and identifying individuals and families at increased risk of developing cancer is one of countless important roles for primary care and other health care providers. Once identified, these individuals can then be appropriately referred for genetic counseling, risk assessment, consideration of genetic testing, and development of a management plan. When medical and family histories reveal cardinal clues to the presence of an underlying familial or genetic cancer susceptibility disorder, further evaluation may be warranted.

Concluding that an individual is at increased risk of developing cancer may have important, potentially life-saving management implications and may lead to specific interventions aimed at reducing risk (e.g., tamoxifen for breast cancer, colonoscopy for colon cancer, or risk-reducing salpingo-oophorectomy for ovarian cancer). Information about familial cancer risk may also inform a person’s ability to plan for the future (lifestyle and health care decisions, family planning, or other decisions). Genetic information may also provide a direct health benefit by demonstrating the lack of an inherited cancer susceptibility. For example, if a family is known to carry a cancer-predisposing mutation in a particular gene, a family member may experience reduced worry and lower health care costs if his or her genetic test indicates that he or she does not carry the family’s disease-related mutation. Conversely, information about familial cancer risk may have psychological effects or social costs (e.g., worry, guilt, or increased health care costs). Family dynamics also may be affected. For instance, the involvement of one or more family members may be required for genetic testing to be informative, and parents may feel guilt about passing inherited risk on to their children.

Knowledge about a cancer-predisposing mutation can be informative not only for the individual tested but also for other family members. Family members who previously had not considered the implications of their family history for their own health may be led to do so, and some will undergo genetic testing, resulting in more definitive information on whether they are at increased genetic risk. Some relatives may learn their mutation status without being directly tested, for example, when a biological parent of a child who is a known mutation carrier is identified as an obligate carrier. Founder effects may result in the recognition that specific ethnic groups have a higher prevalence of certain mutations, knowledge that can be either clinically useful (permitting more rational genetic testing strategies) or potentially stigmatizing. Testing may reveal the presence of nonpaternity in a family. There is the theoretical possibility that genetic information may be misused, and concerns about the potential for insurance and/or employment discrimination may arise. Genetic information may also affect medical and lifestyle decisions.

About PDQ and This Cancer Information Summary

PDQ is the National Cancer Institute's (NCI's) comprehensive cancer information database. PDQ is provided as a service of the NCI. The NCI is part of the National Institutes of Health, the federal government's focal point for biomedical research. The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. The PDQ cancer information summaries are developed by cancer experts and reviewed regularly. PDQ Cancer Genetics Overview