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Family History and the Genetic Risk of Cancer

Up to 15% of all cancers have a familial basis. That means that the cancer tends to occur among members of a family. Much of the time, different types of cancer occur apparently by chance, or in association with common family habits such as cigarette smoking. However, studies have suggested that certain cancers can occur to excess in some families. For example, a woman whose mother and/or sisters (first-degree relatives) had breast cancer is 2-3 times more likely to develop breast cancer than a woman whose close female relatives have not had breast cancer. Many other cancers are associated with having a family history of that cancer. Breast, ovarian, prostate and colon are some of these cancers. There are genetic tests for breast, colon and melanoma available ( genetics counselors here.)  Myriad now has a panel that will test for 25 genes associated with cancer (go here and here)

Genetic mutations that can be passed along to new generations (germ line mutations) would cause familial cancers where family history is important. Most cancers are caused by genetic mutations that occur after birth (somatic cell mutations) and not inheritable (see cancer genomics below) and read the NCI section on cancer genetics here.

Cancer Genomics. The management of cancer is shifting to targeted therapy based on the specific gene mutations that have occurred in the cancer, For instance with adenocarcinoma of the lung if there is an EGFR (epidermal growth factor) mutation then the targeted drug erlotinib (Tarceeva) would be used and for individuals with fusion of the ALK Gene (Anaplastic Lymphoma Kinase) would be treated with crizotinib (Xalkori). The NIH has a site (The Cancer Genome Atlas) to keep researchers up to date on the rapid changes in this field. To understand the genetic basis of cancer go here.
Most cancers are caused by a variable mix of heredity and environmental factors. Cancers, such as lung cancers in cigarette smokers, while caused primarily by external factors, are still influenced by genes that modify an individual's risk of disease. Scientists are currently studying the complex ways in which genes and environment interact. Family clusters of cancer development have been reported for virtually every form of cancer. In general, close relatives of a cancer patient have an increased risk for developing the same type of cancer. An inherited susceptibility often becomes apparent when cancers of the same body site or organ occur in multiple blood relatives. In familial cancers avoiding harmful exposures can help prevent or delay the onset of cancer. For example, members of melanoma-prone families who avoid significant ultraviolet radiation exposure can reduce substantially their risk of melanoma.

Several tumor suppressor genes have been identified, predominantly through studies of cancer-prone families with hereditary cancers. Major recent genetic discoveries include the identification of BRCA1, a gene for hereditary breast and ovarian cancer, the localization of BRCA2 and another breast cancer gene. Approximately 5 percent of breast or colon cancer patients might carry one or more inherited susceptibility genes. The discovery of these genes has increased greatly the numbers of cancer susceptibility gene carriers who can possibly be identified. For detailed information about genetics, and genetic testing go to the NCI site here and for more on breast cancer go here.

Scientists believe that most cancers are caused by a series of genetic mutations that develop over a person's lifetime. However, some cancers are associated with a single inherited gene mutation (e.g., BRCA1 or 2). Researchers believe these mutations account for approximately 5% to 10% of all cancer cases of the genes mapped so far. go to the the ASCO site on genetics here. Other sites:  Atlas,  NCCN Site, PubMed, GeneTests, ACS
The general clinical features that raise the suspicion of a familial form of cancer susceptibility in a patient diagnosed with any type of malignancy include:
  • A cancer that occurs at an unusually young age compared with its usual presentation
  • The development of multiple tumors in a single organ, or bilateral development in tumors in paired organs
  • The development of more than one primary tumor of any type
  • A family history of cancer of the same type in one or more first-degree relatives
  • A high rate of cancer occurrence in the family
  • Cancer occurring in an individual or within a family with congenital anomalies or birth defects

How genes cause cancer

When working properly, genes promote a normal, controlled growth of cells. When the gene becomes altered (mutated), cancer can develop. A mutated gene may tell a cell to produce an abnormal, nonfunctional protein. This abnormal protein may be beneficial, harmful, or may have no effect on the cell.

There are two basic kinds of genetic mutations. If the mutation is passed from one of the parents to the child, it is called a germline mutation. When a germline mutation is passed on from parents to child, it is present in every cell of the child's body, including the reproductive sperm and egg cells. Because the mutation affects reproductive cells, it is passed from generation to generation. Germline mutations are responsible for less than 15% of cancer cases. This is also called familial (occurring in families) cancer.

Most cancer cases are caused by a series of genetic mutations that develop during a person's lifetime. These mutations are called acquired mutations because they are not inherited. Rather, acquired mutations could be caused by environmental factors, such as exposure to toxins or cancer-causing agents. This type of cancer is called sporadic cancer. Most scientists believe that cancer happens when several genes of a particular group of cells become mutated. Some people may have more inherited mutations than others. So, even with the same amount of environmental exposure, some people are simply more likely to develop cancer.

Genes that play a role in cancer

Tumor suppressor genes and oncogenes are considered to be the two main types of genes that potentially cause cancer.

Tumor suppressor genes. These are protective genes. Normally, they suppress (limit) cell growth by monitoring the rate at which cells divide, repairing mismatched DNA, and controlling cell death. When a tumor suppressor gene is mutated (due to heredity, environmental factors, or as part of the aging process), cells continue to grow and can eventually form a tumor. Close to 30 tumor suppressor genes have already been identified, including BRCA1, BRCA2, and p53. In fact, nearly 50% of all cancers involve a missing or damaged p53 gene.

Oncogenes. These are mutated versions of proto-oncogenes. Proto-oncogenes normally determine the rate at which healthy cells divide. When these genes are mutated in the right way, cells can divide quickly and tumors may form because nothing is controlling how the cells grow. Several oncogenes have already been identified, such as HER2/neu and ras.

The process of cancer involves many genes

In order for cancer to develop, several genes in a cell need to become mutated in a way that overrides the checks and balances of the cell. Some of these mutations are inherited and some are acquired. Different genes may also interact in unpredictable ways with other genes or factors in the environment to cause cancer. The goal of new cancer therapies is to reverse the effect of mutations to tumor suppressor genes and oncogenes. Scientists and doctors continue to discover new genes that may play a role in cancer.