Hereditary cancer syndromes
Hereditary cancer syndromes are genetic conditions that increase an individual's risk of developing certain types of cancer, passed down from parents to children through defective or altered genes. While they account for only 5 to 10 percent of all cancers, those with hereditary cancer syndromes may have up to a 90 percent risk of developing cancer. Notable hereditary cancers include breast, ovarian, colon, and melanoma, often linked to specific gene mutations such as BRCA1, BRCA2, and APC. Family histories marked by early cancer diagnoses, multiple cancer types, or several relatives affected by the same cancer can indicate a hereditary risk. Genetic counseling and testing play crucial roles in identifying at-risk individuals and informing them about their options for preventive measures, early screening, and lifestyle changes. These processes not only help in understanding individual cancer risks but also raise ethical considerations regarding privacy and decision-making within families. Enhanced education and research continue to improve detection and management strategies for those affected by hereditary cancer syndromes.
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Subject Terms
Hereditary cancer syndromes
ALSO KNOWN AS: Familial cancer syndromes
DEFINITION: Hereditary cancer syndromes are a group of cancers that develop from an inherited defective or altered gene that passes from parents to children through generations. Scientists have discovered familial genes responsible for hereditary breast, ovaries, and colon cancers. Researchers also believe that prostate and other types of cancer, such as melanoma skin cancer, may have a hereditary component.
Incidence: Hereditary cancers account for only 5 to 10 percent of all cancers in the population. However, individuals with these syndromes are at higher risk, up to 90 percent of developing cancer.
Risk factors: When several cancer cases occur in one family, heredity is not always the cause. Factors such as lifestyle (diet, exercise, tobacco use), carcinogen exposure, or hormonal factors may be the cause. However, sometimes cancer is linked to heredity. Factors that indicate a risk for hereditary cancer include a family member who developed cancer at a young age (under the age of fifty for colon cancer, under forty-five for breast or ovarian cancer), more than one type of cancer in the family, more than two family members with the same kind of cancer, a family member with more than one type of cancer, and cancer in organs that occur in pairs (such as breasts, ovaries). Well-defined hereditary cancers include breast, ovarian, colon, and melanoma.
Breast and ovarian cancers: Hereditary breast and ovarian cancer syndrome (HBOC) results from an alteration (mutation) in the BRCA1 or BRCA2 genes. Men who have the BRCA1 gene alteration are at increased risk for developing prostate cancer. Scientists also believe that those who carry the BRCA1 gene have an increased risk of developing colon cancer.
The BRCA1 gene is believed to be responsible for as many as half of the cases of inherited breast cancer. In high-risk families, an individual may have up to a 50 percent chance of inheriting an altered or mutated copy of this gene. A person who does inherit the BRCA1 gene is at increased risk (up to 85 percent) of developing breast cancer. The BRCA2 gene is responsible for about 35 percent of inherited breast cancers in women.
Women with an inherited BRCA1 gene also have up to an 85 percent chance of developing ovarian cancer by the age of eighty-five. Notably, genetically linked ovarian cancer usually occurs early in life before forty-five.
Colon cancers: Colon cancers involving inherited gene mutations account for 5 percent of all colon cancers. There are several different forms of familial colon cancer, but the most common are hereditary nonpolyposis colon cancer (HNPCC) and (FAP).
Four specific genes (MLH1, MSH2, PMS2, and MSH6) have been identified in HNPCC. Individuals who carry one or more of these genes have an 80 percent risk of developing colon cancer.
FAP, also known as familial polyposis coli or adenomatous polyposis coli, accounts for less than 1 percent of all colon cancers. A mutation of the APC gene is responsible for this syndrome. FAP can begin as early as age ten. More than 90 percent of people with FAP develop colon cancer by the age of fifty.
Familial melanoma: In familial melanoma, there is a genetic mutation of the following genes: CDKN2, CDK4, and MCR1. In this cancer syndrome, at least two first-degree relatives have a history of invasive melanoma skin cancer. The person at risk usually develops from ten to one hundred moles, usually on the upper trunk and arms. These moles, known as dysplastic nevi, are different in shape, color, and symmetry from normal moles and are present at a young age.
Other hereditary syndromes associated with cancer include:
- Cowden syndrome (CS) associated with uterus and thyroid cancer; PTEN gene mutations
- Lynch syndrome or Hereditary Non-polyposis Colorectal Cancer Syndrome associated with colorectal cancer and uterine cancer; DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2
- Hereditary Leukemia and Hematologic malignancy syndromes associated with myeloid leukemia
- Familial adenomatous polyposis (FAP) or Gardner's Syndrome associated with colon cancer; APC gene mutations
- Li-Fraumeni Syndrome (LFS) associated with breast, lung, brain, adrenal, and bone cancers; TP53 gene mutations
- Von Hippel-Lindau disease (VHL) associated with kidney cancer; VHL gene mutations
- Multiple endocrine neoplasia (MEN) MEN1 and MEN2 cause thyroid, pituitary, parathyroid, and pancreas cancers
Prevention, education, and screening: Researchers continue to study hereditary cancer syndromes to identify other gene alterations responsible for certain types of cancer. These discoveries will reduce cancer deaths because they will allow identification of those at risk, early diagnosis, and treatment.
Many hospitals have cancer centers with hereditary cancer programs, which include education, genetic testing, genetic counseling, research, and clinical management of high-risk individuals. It provides clinical services to families, including medical evaluations, consultations with a clinical geneticist, and cancer screenings.
Technological advancements allowed the discovery of defective genes that cause breast, colon, ovarian, and other cancers. Education of the public and community physicians is important to help identify genetic mutation carriers and noncarriers within families.
Genetic counseling involves a clinical geneticist and a genetic counselor. Their job is to review several generations of a family’s medical history, construct a medical family tree, and conduct a clinical exam to evaluate a person’s current health status and look for any physical clues regarding that person’s expression of genetic disease. Genetic counselors also provide individuals with information needed to understand their potential risk for an inherited cancer and to help them decide whether to undergo genetic testing.
Genetic testing normally involves a simple blood test or sample of cells taken from healthy individuals who are members of high-risk families. The tests help determine an individual’s cancer risk. Individuals with a strong family history of cancer who receive a cancer diagnosis may also benefit from genetic testing. Genetic testing can help physicians and patients learn if other cancers are likely to develop. For example, inherited genes that play a role in the development of colon or breast cancer also play a role in the development of stomach, uterine, and ovarian cancer.
Patients and physicians can work together to plan a screening schedule that will enable the detection of cancer in its earliest, most treatable stage when the chance of cure is highest.
Perspectives and prospects: For those who are members of high-risk families, a negative result from genetic testing for hereditary cancer genes can be a relief. They can avoid undergoing unnecessary rigorous cancer screening and other tests.
If genetic testing results are positive, this knowledge helps people make decisions concerning follow-up care, preventive strategies, and lifestyle changes. They may decide on a surgical intervention after speaking with their physician and genetic counselor. For example, if a genetic test is positive for the hereditary gene for ovarian cancer, a woman may have surgery to remove the ovaries to minimize her risk.
Some aspects of genetic testing involve ethical, legal, and social issues. Genetic testing, counseling, and screenings may be part of standard clinical protocol management for common hereditary cancers. However, healthcare insurance companies and other practitioners may not be willing to support testing for less common types. If a family is considered at risk for hereditary cancer syndromes, its members will need to decide whether to have genetic testing. The decision to undergo genetic testing can be complex, and some family members may differ. Privacy of test results for an individual family member and other members’ rights to know those results may also be an issue.
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