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Cancer is now clearly understood to be a disease of abnormal gene function. Genes are segments of DNA that contain instructions on how to make the proteins the body needs to function. They govern hereditary traits, such as hair color, eye color, and height, as well as susceptibility (likelihood of being affected) to certain diseases, such as cancer.
In humans, genes are located on 23 pairs of chromosomes. One of each chromosome pair comes from the mother, the other from the father. Each chromosome can contain hundreds or thousands of genes that are passed from the parents to the child. The genes you were born with are in every cell of your body.
We now understand that genes serve 2 major roles in cancer: some contribute to the development of cancer and others stop cancer from developing or growing. Genes that can cause cancer are called oncogenes. Genes that stop or suppress cancer growth are called tumor suppressor genes. (For more information, refer to the document,
"Oncogenes and Tumor Suppressor Genes.")
Even if you were born with healthy genes, some of them can become changed (mutated) over the course of your life. For example, exposure to large doses of radiation can cause changes in the genes of some of the body’s cells and allow cancer to start. This explains why most cancers are not inherited but arise from gene mutations you acquire during your life. The older you get, the more gene mutations you may accumulate. This is why cancer risk increases with age. In contrast, cancers that are inherited tend to occur earlier in life than cancers of the same type that are not inherited.
Cancer is such a common disease, especially in older adults, that many families have at least a few members who have had cancer. Only about 5% to 10% of all cancers are the inherited type. The cancer actually is not inherited, but the abnormal gene that can cause the cancer is what is inherited. This document will focus on those cancers that tend to occur in families.
Most of the time, different types of cancer occur apparently by chance or are linked with common family habits such as cigarette smoking, which can damage the genes in the lungs, throat, mouth, and several other organs. However, studies have shown that certain cancers can occur to excess in some families. For example, a woman whose mother, sister, or daughter (first-degree relatives) has had breast cancer is about twice as likely to develop breast cancer as a woman whose close female relatives have not had breast cancer.
Some of these women have an inherited gene mutation that is linked to higher rates of breast or ovarian cancer. Women with first-degree relatives who have had breast cancer may choose to undergo genetic testing to find out if they have a breast cancer gene mutation. If a mutation is present, the woman has a high chance (or risk) of developing breast cancer before age 40. She may start getting mammograms at a younger age, have special breast cancer screening tests, or take other measures to detect cancer earlier and reduce her chance or risk of getting breast cancer.There are 2 known breast cancer genes. Mutations of the BRCA1 gene are linked to breast and ovarian cancer. Individuals who have these gene mutations also have an increased risk of colon and prostate cancer. BRCA2 gene mutations are related to a higher risk of breast cancer, as well as pancreatic and ovarian cancer, in both men and women.
A few types of childhood cancers are known to occur more often in some families. Researchers learned about how tumor suppressor genes work through their study of retinoblastoma, a childhood cancer that starts in the eye. About 40% of children with retinoblastoma have inherited an abnormal Rb tumor suppressor gene from one parent. About 85% of children who inherit an abnormal Rb gene from a parent develop a retinoblastoma in one or both eyes.
When children inherit Rb mutations from a parent, the mutation is present in every cell of the child's body and, therefore, can be detected by testing DNA of blood cells. Because every person has 2 Rb genes but passes only one of each to their children (the second gene comes from the other parent) the odds that a parent will pass his or her mutated gene on to a child are 1 out of 2. Family studies have shown that retinoblastoma is inherited (or passed by genetic transmission from parent to child) in about 45% of the cases. Even though the child inherited only 1 of the pair of chromosomes or genes for retinoblastoma, he or she is likely to have the disease. This is because there is no backup to stop the mutated gene from making abnormal cells if the healthy Rb gene stops working in even one cell. Patients with the hereditary form of retinoblastoma also have an increased lifetime risk of developing other types of cancer, including osteosarcoma (bone cancer) of the leg and the orbit (bone around the eye).
Another example of hereditary cancer risk occurs when a person inherits a mutation in the p53 gene. A normal P53 gene stops the growth of abnormal cells. People with a p53 gene abnormality have a higher risk of breast cancer, sarcoma, leukemia, and tumors of the adrenal gland and central nervous system. This condition is called Li-Fraumeni syndrome. One study showed that 15% of Li-Fraumeni patients who had cancer were diagnosed later with a second cancer, and some developed a third and fourth cancer later on.
Many other cancers are associated with having a family history of that cancer. Breast, ovarian, prostate, and colon are some of these cancers. Please refer to the specific Cancer Site documents on our website for more information about a particular type of cancer and its genetic components.
Precancerous Diseases
In addition to the family cancer patterns, several uncommon types of cancerous and/or precancerous conditions show heredity patterns. Some of the more common syndromes are discussed below.
An important precancerous condition among adults is Familial Adenomatous Polyposis (FAP) of the colon, which is characterized by hundreds of polyps in the colon. Without treatment, at least one of these polyps will almost certainly become cancerous. But if the trait of multiple polyposis is diagnosed early in life, surgery to remove the colon can prevent the development of cancer.
Another major inherited syndrome that increases a person’s risk for colon cancer is called hereditary non-polyposis colorectal cancer or HNPCC. Individuals with this syndrome have up to an 80% lifetime risk of colorectal cancer. Most of these cancers occur before age 50. HNPCC accounts for 1% to 5% of all colorectal cancers, and can also cause endometrial cancer (inside the uterus) in women.
The most common type of neurofibromatosis (a syndrome that includes tumors of the nerves) shows up in childhood as dark areas on the skin, which are called café au lait spots. Children with neurofibromatosis are more likely to have neurofibromas of the skin; cancers of the eye, muscle, or kidney; and sarcomas and leukemias. About half of these cases are hereditary.
Several types of endocrine system (hormone or glandular organs) syndromes are known. People with the multiple endocrine neoplasia syndrome type 1 (MEN1) have a high risk of developing tumors of 3 glands – the pituitary, parathyroid, and pancreas. The multiple endocrine neoplasia syndrome type 2 (MEN2) increases the risk of parathyroid, adrenal, thyroid, and nerve tumors.
Some families have unusual moles on their skin, called dysplastic nevi, which are linked to a higher risk of melanoma. The genetic basis of precancerous moles that run in families was recently identified as a gene called CDKN2A.
Families with xeroderma pigmentosum (a very rare skin disorder) tend to develop multiple skin cancers at an early age. They are extremely sensitive to the cancer-promoting effects of sunlight because of a defect in the enzyme that helps skin cells repair DNA damage caused by ultraviolet light. People with this disorder may also have more internal cancers.
Down syndrome is a known genetic defect that is linked to leukemia.
Defects of the immune system, including genetic diseases such as Wiskott-Aldrich syndrome and agammaglobulinemia, increase the risk of developing lymphoma. Other syndromes exist, though most of them are rare.
Genetic Counseling and Testing
Individuals with a strong family history of cancer or multiple types of cancer may want to find out about their genetic makeup. This knowledge may help the individual or family members in planning health care for the future. Since inherited mutations affect all cells of a person's body, they can often be identified by genetic testing on blood samples. Genetic counseling and testing may be recommended for some people with a strong family history of cancer.
For more information on genetic testing, please call us at 1-800-ACS-2345 and request a copy of
the American Cancer Society document, “Genetic Testing – What You Need to Know.”
Future Directions
The Human Genome Project is an international program devoted to determining the complete DNA sequence in humans. Although all the genes have been listed, there is still a great deal to learn about what proteins each gene makes. Researchers need to find out how each gene fits into the body’s activities at the cellular level and the effect that activity has on diseases such as cancer.The hope is that it will provide a single reference to all human genetic information, including cancer genes and markers. The impact this project will have on the future of cancer is profound. You can read more about the Human Genome Project on the Web at
http://www.genome.gov
Genetics Dictionary
- chromosome (krom-o-some): structures that carry the genes, the basic units of heredity. Humans have 23 pairs of chromosomes, one member of each pair from the mother, the other from the father. Each chromosome can contain hundreds or thousands of individual genes.
- gene: a segment of DNA that contains information on hereditary characteristics such as hair color, eye color, and height, as well as susceptibility to certain diseases. Genes contain instructions on how to make the proteins the body needs to function, when to destroy damaged cells, and how to keep the cells in balance.
- hereditary cancer syndrome: conditions associated with cancers that occur in several family members because of an inherited, mutated (abnormal) gene.
- oncogenes (on-ko-genes): genes that promote uncontrolled cell growth and multiplication. After activation, they can cause cells to grow too quickly and form tumors.
- tumor suppressor genes: genes that monitor cell division, repair damaged DNA, or cause cells to die at the appropriate time. Alterations of these genes can lead to rapid cell growth and development of cancer.
Additional Resources
More Information From Your American Cancer Society
We have selected some related information that may also be helpful to you. These materials may be viewed on our Web site or ordered from our toll-free number, 1-800 ACS-2345.
National Organizations and Web Sites
In addition to the American Cancer Society, other sources of patient information and support include*:
National Cancer Institute
Telephone Number: 1-800-4-CANCER
Internet Address: www.cancer.gov
*Inclusion on this list does not imply endorsement by the American Cancer Society.
The American Cancer Society is happy to address almost any cancer-related topic. If you have any more questions, please call us at 1-800 ACS 2345 at any time, 24 hours a day.
References
American Cancer Society. Cancer Facts and Figures 2008. Atlanta: American Cancer Society, 2008.
National Institutes of Health. Chromosome Abnormalities Fact Sheet. Available at National Human Genome Research Institute at http://www.genome.gov/11508982. Accessed 11/10/04
Taub JW. Down syndrome and leukemia &ndash it’s in the cards. Blood. 2004;103:2434.
Chaudru V, Chompret A, Bressac-de Paillerets B, et al. Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families. J Natl Cancer Inst. 2004; 96:785-95.
Kufe DW, Pollack RE, Weichselbaum RR, et al. Cancer Medicine. 6th Ed. Lewiston NY, 2003.
Abeloff MD, Armitage JO, Lichter AS, Niederbuber JE. Clinical Oncology 2nd ed. New York, NY: Churchill Livingstone; 2000.
DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia, PA: Lippincot, Williams, and Wilkins;2001.
Revised: 03/09/2005
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