In a broad sense, all cancers are genetic because they involve changes (mutations) in the cells’ DNA. Normally the cells of the body are programmed to grow, live and die in a controlled manner. The body can also repair some tissues or DNA that is damaged. However, when cells cannot repair damaged DNA, they grow out of control and can become malignant.
Some diseases are caused by a specific mutation to a specific gene. However, most cancers do not have a direct cause-and-effect relationship with gene mutations. Most cases of cancer with gene mutations may have multiple mutations that may require other mutations or environmental conditions to become active. These mutations can be acquired or hereditary.
Acquired mutations account for most cancers. They often take years to produce cancers. Hereditary mutations are much rarer, accounting for about 5 to 10 percent of cancers. These mutations are present in all the cells at birth, and thus may lead to the development of cancer earlier in life.
Some types of cancer can occur in families with above-average frequency. However, this does not mean a hereditary mutation is involved. For example, a family may have a higher-than-normal rate of smoking, tend to eat a lot of meat, be physically inactive or live near an environmental hazard such as a toxic dump. These factors can increase the risk of cancer without genetic involvement. In many individuals, an increased rate of cancer may be a coincidence.
Genetic mutations can harm, have no effect on or even help a person’s health. The greatest genetic risk associated with cancer involves two types of genes. Oncogenes are acquired or hereditary mutations that cause normal cells to grow out of control and become cancerous. Tumor suppressor genes are normal, helpful genes that control cell division, repair damaged DNA and destroy cells that cannot be repaired. If acquired or hereditary mutations inactivate tumor suppressor genes, cancer can result.
Genetic tests are currently available to identify some oncogenes, and additional genetic tests are being developed. Genetic tests for individuals involve laboratory assessment of samples of blood or other bodily substances obtained from patients. A physician may recommend such tests if an individual has a strong family history of cancer. It is important to note that a positive test result can indicate an increased risk of cancer, not that a person definitely will develop the cancer. These tests can encourage individuals to take precautions to reduce the risk of cancer, such as:
Getting a mammogram, prostate examination, colorectal screening or other appropriate test at an earlier age or more often than the standard recommendation for the general population.
Making beneficial lifestyle changes to reduce the risk of cancer, such as improving diet, increasing exercise and quitting smoking.
Taking preemptive medical action, such as surgery or chemotherapy. For example, people with an inherited condition in which there are hundreds of colon polyps often have colon surgery to prevent colorectal cancer. Women who have a mutation of the BRCA gene may choose to have prophylactic mastectomy to prevent breast cancer.
Genetic testing can have profound psychological effects and influence family-planning decisions. Test results are hard for most patients to interpret. Experts recommend that genetic counseling accompany such assessments.
In recent years genetic research has made great progress, which is expected to accelerate. Gene therapy, the use of healthy genes to repair damaged cells, is being developed to treat cancer and other conditions. Thousands of people, the majority of them Americans, have taken part in clinical trials of gene therapy, mostly for cancer. The U.S. Food and Drug Administration (FDA) has not yet approved the sale of gene therapy products, but scientists expect that eventually such innovations will be able to help fight and prevent cancer.
About genetics & cancer risk
All types of cancer involve genes. Cancer begins when cells grow uncontrollably. This growth is controlled or not controlled by instructions from the genes. When genes are damaged, or mutated, these instructions may be incorrect or incomplete and lead to tumor formation.
All aspects of the genetic risks of cancer begin in the biology of the body. All cells have chromosomes, the structures that contain genetic information that enable cells to function and reproduce. In humans, most cells contain 46 chromosomes in 23 pairs: 22 pairs of autosomal chromosomes and one pair of sex chromosomes. In these chromosome pairs, one chromosome comes from the mother and one from the father. The autosomes have similar information regardless of the parent and produce the coding for eye or hair color, height and all other aspects of human development.
Egg and sperm cells contain only 23 chromosomes: 22 autosomes and 1 sex chromosome, either X or Y. Each person receives an X chromosome from the mother's egg. A father's sperm may contribute an X or a Y chromosome. When the father contributes an X chromosome, the child has two X chromosomes and is a girl. If the father contributes a Y chromosome, the child has one X and one Y chromosome and is a boy.
Each chromosome contains DNA, the complex substance that contains genetic information and provides the instructions for all processes in the cells. An area of DNA that contains instructions for specific proteins is called a gene, the basic unit of heredity. The entire collection of genes in humans is called the human genome. Researchers estimate that there are 20,000 to 25,000 genes in the human genome. Genes have specific locations on chromosomes. For example, researchers estimate that chromosome 13 contains between 300 and 700 genes. In one section of chromosome 13, missing areas, or deletions, in a gene called RB1 may be responsible for some cases of retinoblastoma, an eye cancer that usually affects children.
Like chromosomes, genes also occur in pairs. Genes may be dominant or recessive. If a gene is dominant, one mutated copy of the gene can affect its expression. It need only be inherited from one parent. Many cancer-predisposing mutations involve this type. When a gene is recessive, a person needs both copies of the mutated gene (one from each parent) to express the condition. The exception involves the X chromosome. A male carrying mutation that affects the X chromosome will have the mutation condition because males only have one X chromosome. A female carrying only one X mutation will be unaffected but will be a carrier, a person who has one recessive gene for a disease.
The body has two main types of genes that influence cancer risk:
Oncogenes are acquired or hereditary mutations that cause normal cells to grow out of control. In normal function, these genes direct cell growth. When their DNA is damaged or mutated, they stay “turned on” and tell a cell to continue to grow without stopping. In such situations, the oncogene may promote the growth of a tumor.
Tumor suppressor genes are normal, helpful genes that control cell division, repair damaged DNA and destroy cells that cannot be repaired. Acquired or hereditary mutations can inactivate tumor suppressor genes, which means they do not stop cell growth and a tumor may develop. Inherited abnormalities of tumor suppressor genes cause many of the hereditary cancers.
Researchers have identified more than 100 oncogenes and about 30 tumor suppressor genes and continue their attempts to discover more of these genes. Scientists are only beginning to understand the complexity of the genetic aspects of cancer. For example, one of the identified tumor suppressor genes is known as p53, In normal function, the p53 protein binds with DNA and stimulates another gene to produce a different protein (called p21), which stops cell division. If p53 is damaged, all the remaining steps in the process cannot occur and p21 is not produced to stop cell division. The cells grow uncontrollably. The p53 gene mutation has been associated with several cancers. including bladder cancer and breast cancer. When one entire copy of the p53 gene is not functioning, the person is predisposed to several cancers, a condition known as Li-Fraumeni syndrome.
Most people may carry 5 to 10 gene mutations in their cells, according to the American Academy of Family Physicians. These mutations may cause no problems. Diseases such as cancer may occur if a person has a dominant disease gene, two recessive genes for the disease, or mutations that interact with each other or the environment.
Even in cancers that can be linked to an environmental conditions, such as exposure to tobacco smoke or radiation, the environment damages the tissue and genetic material to initiate the tumor growth. The genetic risk associated with cancers lies in the inheritance or mutation of genes that make a person more likely to develop a certain type of cancer. In this sense, all cancers are genetic. Some types of cancer can occur in families with above-average frequency. However, this does not mean a hereditary mutation is involved. Genetic mutations can harm, have no effect on or even help a person’s health. The cells usually but not always recognize and repair acquired mutations.
Recently, researchers have completed a “map” of the genes associated with breast and colon cancer tumors. After analyzing more than 13,000 genes from tumors, the study showed that each type of cancer had about 100 different genes with mutations. Continuing research to identify which mutations affect cancer may provide information about effective treatment and new types of therapies to repair the gene damage or stop the progress of the cancer.
Family history and cancer
A family history is typically a part of a physician's examination. It is obtained through a series of questions that focus on health and social issues. It is especially important for people with a strong familial history of cancer.
According to the National Cancer Institute (NCI), indicators of inherited risk of cancer include the following:
Clustering of the same type of cancer in close relatives (parents, siblings, children)
Two or more primary cancers in one relative
Onset of cancer at an earlier than usual age in one or more individuals
Cancer in the sex not usually affected (e.g., breast cancer in men)
Evidence of autosomal dominant inheritance
Bilaterality in paired organs (e.g., both lungs or both ovaries are affected)
Patterns of cancer in the family that are associated with a known cancer syndrome or with other diseases
When hereditary cancer is suspected, the physician may have the patient collect information for a more detailed family history called a pedigree (also called a family tree). This chart of family relationships tracks patterns of the transmission of disease.
The NCI recommends the following if there appears to be a high family risk of cancer:
A cancer family history that includes:
Relatives on the mother’s side and the father’s side, including those without cancer
Noting of nonpaternity, consanguinity (marrying among close blood relatives) and use of assisted reproductive technology such as donor egg or sperm
Race, ancestry, and ethnicity information for all grandparents
Seemingly unrelated conditions, such as birth defects
Second-degree relatives (grandparents, aunts and uncles, nieces and nephews, grandchildren)
Third-degree relatives (cousins, great aunts, great uncles, great grandparents) who have had cancer or have had a first-degree relative afflicted with cancer
Collecting the following information for any relative who has cancer:
Type of each primary cancer
Age of diagnosis for each primary cancer
Where this person was diagnosed and treated
Current age, or age at death and cause of death
Exposure to carcinogens (such as smoking or radiation)
Other significant health problems
Collecting the following information for any relative who does not have cancer:
Current age, or age at death and cause of death
Any surgeries that reduce the risk for cancer
Whether the person has had routine screening for cancer
Any nonmalignant features of the syndrome in question
Exposure to carcinogens
Other significant health problems
This information may be used to help determine whether a family may have a hereditary cancer syndrome, what the most likely diagnosis is if a syndrome is indicated, and how the genetic traits are passed down in the family (dominant, recessive or X-linked). Answering these questions can help individuals make a more informed decision on whether to take precautionary measures and whether to undergo genetic tests and genetic counseling.
The information may also help a physician determine when a patient should undergo certain screening tests. For example, women at average risk for breast cancer should begin screening mammograms at age 40. If a woman has breast cancer in her family or is known to have a gene mutation associated with the disease, her physician may recommend that mammograms begin at an earlier age and with greater frequency.
Hereditary cancer syndromes
Hereditary cancer syndrome is a term used when several members of a family have cancer because of an inherited abnormal (mutated) gene. Increased risk of cancer is associated with hundreds of hereditary conditions, according to the National Cancer Institute(NCI).
Some of the more prominent of these include:
Breast cancer. About 5 to 10 percent of breast cancers are associated with known mutated genes, especially the BRCA1 and BRCA2 genes. These mutations can raise the lifetime risk of breast cancer by 80 percent, according to the American Cancer Society (ACS). Some of these mutations have also been found to increase the odds of getting ovarian cancer. In addition, men with BRCA1 mutations have an increased risk of developing prostate cancer. Other genes have also been identified that may increase the risk of breast cancer.
Familial prostate cancer. Male carriers of the two main gene mutations involved in hereditary breast cancer have three to four times the risk of prostate cancer. Other gene mutations have also been implicated in prostate cancer.
Hereditary causes of colorectal cancer, including hereditary nonpolyposis colon cancer (HNPCC) and familial adenomatouspolyposis (FAP). These conditions, featuring polyps that may become malignant, are estimated to account for up to 15 percent of cases of colorectal cancer. Sometimes people with such conditions have the colon surgically removed as a preemptive measure.
Familial melanoma. Several melanoma-predisposing autosomal dominant genes have been identified. An estimated 5 to 7 percent of people with melanoma come from genetically high-risk families.
Neurofibromatosis. Type 1 affects one person in 4,000 and involves skin discoloration and tumors that become malignant in up to 5 percent of case. People with type 1 have a higher risk of developing other cancers, such as brain tumors and leukemia. Type 2 affects one person in 50,000 and often affects the acoustic (hearing) nerve. Surgery may be needed with type 2 to avoid loss of hearing.
Fanconi’s anemia. An autosomal recessive condition associated with about 20 percent of case of childhood aplastic anemia. It is more common in Ashkenazi Jews. Multiple birth defects are common. Signs include bleeding, anemia and easy bruising. Average age of diagnosis is 6 years.
Family cancer syndromes also have been found in other forms of cancer, including:
Brain tumors
Hodgkin’s lymphoma
Kidney cancer
Melanoma
Pancreatic cancer
Retinoblastoma
Testicular cancer
Thyroid cancer
Scientists are working on identifying, treating and preventing hereditary cancers. Progress has accelerated since the Human Genome Project was completed in 2003. This international effort included identification of all human genes. Scientists at the National Institutes of Health are attempting to create a Cancer Genome Atlas to identify all the genes in cancer. The project will begin by studying three cancers: glioblastoma, lung cancer and ovarian cancer. A separate study recently completed at Johns Hopkins University identified 189 genes mutations in breast cancer and colon cancer.
Researchers are using the data to improve genetic tests and gene therapy.
Questions for your doctor about genetics
Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctors or other healthcare professionals the following questions about genetics and cancer:
How can I compile a thorough family history?
Which factors in my family’s history can affect my health?
Do I have a risk of any cancers based on my family background?
What preventive steps can I take to reduce the risks of these cancers?
Which genetic tests might be appropriate for me?
Should other members of my family undergo any genetic testing?
Based on my family history, which cancer screenings should I have and at what age?
What schedule should I use for my cancer screenings?
Should I consider any preventative surgeries or treatments?
