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Life After Cancer A Roadmap for Cancer Survivors

Genetics and Cancer Survivorship
Ernest H. Rosenbaum, MD, FACP

Familial Cancer is caused by a genetic mutation change in the cell's DNA. Gene damage and its relationship to cancer cell growth and maturation can be caused by an inherited or acquired DNA defect. Genetic relationships have been established for breast, endometrial, and colon cancers. It generally takes at least two hits to cause a cell's DNA genetic mutation to initiate the change to a cancer cell. People born with a familial genetic mutation already have the first hit, so an environmental gene damage (e.g., from tobacco, asbestos, diet, or sunlight) can be the second hit, causing the cell to become a cancer cell. Once a cell's DNA has made the initial change to a cancer cell, the cancer cell undergoes multiple, complex genetic and metabolic changes as the cells multiply, grow, and possibly metastasize. Thus, a combination of environmental effects and genetic changes can proceed to develop cancer.

Who Is at a Genetic Risk for Cancer?
Those with a history of being diagnosed with cancer before age fifty
Those who have two or more close relatives or a child, uncle, aunt, or grandparent with one or more cancers diagnosed before age sixty
Those who have three or more relatives with the same or different forms of cancer
Those who have one or more relatives with multiple cancers, such as breast and ovarian cancer

Genetic counseling and testing may be used to evaluate your hereditary history and make appropriate recommendations. Genetic testing is not for everybody; it is designed primarily for those in certain risk categories. Even negative test results do not rule out the chance that a different gene mutation exists but has not been detected. Thus far, no assurance from a negative test is possible.

Patients with a potential hereditary cancer risk can do several things:
Increase surveillance, such as doing mammograms and colonoscopies at an earlier age, and adopt lifestyle modifications, drug therapy (e.g., tamoxifen for breast cancer prevention), and possibly prophylactic breast surgery (mastectomy) to reduce the cancer risk.
Become informed about which surveillance programs are the best options for you.

Genetics and Breast Cancer
More than 90 percent of familial breast cancer cases are caused by DNA mutations in the BRCA1 or BRCA2 oncogenes, which normally become cancerous through interactions with other genes. If a person inherits a BRCA gene mutation, it predisposes her to breast or ovarian cancer. In BRCA carriers, radiation exposure has been found to have an increased effect on breast cancer risk with a greater radiosensitivity, thus women with BRCA1 or BRCA2 genes must be especially cautious about mammograms and radiation exposure, especially after the age of thirty.

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