To date, we know about several genes in which mutations cause a greater risk for cancer. The most significant of these are: RET, PTEN, P53, MYH, APC, MLH1, MSH2, BRCA1, BRCA2. Efforts to identify additional genes and genetic situations involving increased cancer risk are being conducted in cancer laboratories and clinics throughout the world. As of now, we know that the most common cases where hereditary factors could be involved are:
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Breast Cancer - Several genes are involved in a significantly increased risk for breast cancer, and a slightly greater risk for other cancers. The two main genes are called BRCA1 and BRCA2. Women who have mutations in these genes have a risk of up to 50%-80% of developing breast cancer by age 80, and an increased risk of developing ovarian cancer. Mutations in these genes are also involved in greater risk for developing other types of tumors (cancer of the pancreas, prostate, skin, etc.), but in lower percentages. In the Ashkenazic population 3 common mutations have been identified (affecting 2.5% of the population) in the BRCA1 / 2 genes. Mutations have also been identified in other population groups, but they are less common.
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Colorectal Cancer - Approximately 20%-30% of colorectal cancer cases are hereditary, and a genetic background has been identified in some of them. HNPCC (hereditary nonpolyposis colon cancer) Syndrome (or Lynch Syndrome) is the most common of all the genetic syndromes that lead to colorectal cancer. It is responsible for some 3%-5% of the cases of colorectal cancer. Among carriers, the risk of developing colorectal cancer can reach 80%, the risk for uterine cancer can reach 60%, and the risk of developing other tumors outside the gastrointestinal system like ovarian cancer, and tumors in the urinary tract and other organs (skin, brain) may also be increased.
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HNPCC Syndrome is caused by a mutation in genes relating to damage repair of the cell's genetic material (DNA). Genetic clarification regarding the question of HNPCC is usually conducted in several stages: testing the DNA in the tumor, finding specific antibodies in the tumor, and testing for mutations in suspicious genes. Hadassah Hospital has recently set up a clinical and laboratory protocol for carrying out these clarifications. The laboratory test is relatively less expensive compared with the cost elsewhere.
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Another gene that increases a person's risk of colorectal cancer is APC (adenomatous polyposis coli), which is responsible for a rare syndrome known as FAP (familial adenomatous polyposis). If a person has FAP, they are susceptible to the development of dozens (can be up to thousands) of polyps in the colon with a high risk of cancer in the digestive tract.
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Ovarian Cancer - The two principal genes responsible are called BRCA1 and BRCA2. Women carried these mutations have an increased risk of developing ovarian cancer and a high risk of developing breast cancer. In the Ashkenazic population 3 common mutations have been identified (occurring in 2.5% of the population) in the BRCA1/2 genes. Mutations have also been identified in other population groups, but they are less common. It should be noted that roughly 50% of the Ashkenazic women who have had ovarian cancer will be found to have mutations in the BRCA genes.
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Uterine Cancer - In some cases this is caused by mutations in the genes that cause HNPCC (see above - Colorectal cancer).
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Another important gene is P53. An inherited mutation in this gene is quite rare and increases the risk for a condition known as Li-Fraumeni syndrome, which is characterized by a greater risk for various tumors, such as brain tumors, sarcoma or breast cancer. To identify carriers with this genetic mutation it is important to adjust medications and avoid certain types of treatment.
We know of other genes whose mutations also entail greater risk for rare hereditary forms of cancer, such as melanoma, tumors of the endocrine glands, corneal tumors, etc.