Developmental Disorders of the Lymphatics

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Sunday, December 10, 2006

Hereditary versus Spontaneous Cancer

Hereditary Versus Spontaneous Cancer

By Amy Adams, MS

Reviewed by Miriam Komaromy, MD

Last updated March 26, 2001

Cancers are the result of mutations in genes. However, in hereditary cancer some of these mutations are inherited, and in sporadic cancer of the mutations occurred spontaneously.

Sporadic Cancer

In people with sporadic cancer, certain cells in their body developed mutations that led to cancer.

Most cancers are considered sporadic. In people who have sporadic cancer, they did not inherit cancer-causing mutations from their parents. Instead, certain cells in their body developed mutations that led to cancer. These mutations can be caused by sun (which can lead to skin cancer), exposure to radiation or some chemicals, or even random events within the cell.Cancer-causing mutations generally interrupt the function of genes that either keep the cell dividing at a normal rhythm or prevent mutations from accumulating. It usually takes more than one mutation to cause cancer. But if the first mutation occurs in a gene that repairs or prevents other mutations, then additional changes can quickly accumulate. Eventually, the cell has enough mutations that it begins to divide out of control. When this happens, the cell divides rapidly and forms a mass called a tumor. Only the cells within the tumor contain the spontaneous mutations.Researchers are starting to identify genes that are commonly mutated in sporadic cancers. These studies can tell a doctor important things about how the sporadic cancer develops and how it will respond to treatment. However, finding these genes does not provide any information about a person's hereditary cancer risk or the risk of other members of their family.

Hereditary Cancer

In sporadic cancer, only the tumor cells have mutations. In hereditary cancer, every cell in the person's body has a mutation.

People with hereditary cancer inherit a mutated gene from their parents. Every cell in the person's body contains the mutation. Most importantly, cells of the ovaries and testes – which make the sperm and eggs – contain the mutation and can pass that altered gene along to children.It generally takes more than just one mutation to cause cancer. But people who have inherited a mutation are one step closer to cancer than those who haven't. Eventually, additional mutations accumulate in a cell, and that cell begins dividing quickly to form a tumor. In the case of hereditary cancer, the tumor cells usually contain some mutations that aren't found in the rest of the body, but also contain one critical mutation that every cell shares. Because these people were born with a cancer-related mutation, they are more likely to develop cancer and to develop it at a young age than are people who do not inherit a mutation.The genes that cause hereditary cancer are often the same ones that are mutated in sporadic cancers. For example, people with the hereditary cancer syndrome called Li-Fraumeni have a mutation in a gene called p53. Mutations in p53 are also commonly found in sporadic cancers. Again, the difference is that people with sporadic cancers can't pass their mutated p53 gene on to their children, whereas people with Li-Fraumeni can.


Familial Cancer

Familial cancer is caused by a mixture of environmental factors and genetics.

People with familial cancer have one or more cases of cancer in their family, and are at slightly increased risk of developing cancer themselves. However, researchers aren't sure how much of familial cancer is caused by genes, and how much is caused by environmental factors such as diet and exercise.Researchers think that familial cancer may be influenced by as-yet-unidentified genes, whose effects are not fully understood. As with hereditary cancer, these mutations are in every cell of a person's body. But unlike hereditary cancer, carrying mutations in these genes poses only a slight risk of developing cancer.

References

Kinzler, K. and Vogelstein, B. (1996). Lessons from hereditary colorectal cancer. Cell 87: 159-170.Li, F.P. and Fraumeni, J.F. Jr. (1969). Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med. 71(4):747-52.Shattuck-Eidens D. et al. (1997). BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing. JAMA. 278(15):1242-50.

Genetic Health