Family Cancer Syndromes

Cancer is such a common disease that it is no surprise that many families have at least a few members who have had cancer. Sometimes, certain types of cancer seem to run in some families. Sometimes, this is because family members have certain risk factors in common, such as smoking, which can cause many types of cancer. It can also be due in part to other factors, like obesity, that tend to run in families and influence cancer risk.

But in some cases the cancer is caused by an abnormal gene that is being passed along from generation to generation. Although this is often referred to as inherited cancer, what is inherited is the abnormal gene that can lead to cancer, not the cancer itself. Only about 5% to 10% of all cancers result directly from gene defects (called mutations) inherited from a parent. This document focuses on those cancers.

DNA, genes, and chromosomes

Cancer is a disease of abnormal gene function. Genes are pieces of DNA (deoxyribonucleic acid). They contain the instructions on how to make the proteins the body needs to function, when to destroy damaged cells, and how to keep the cells in balance. Your genes control things such as hair color, eye color, and height. They can also affect your chance of getting certain diseases, such as cancer.

Every cell in your body has all of the genes you were born with. Although all cells have the same genes and chromosomes, different cells (or types of cells) may use different genes. For example, muscle cells use a different set of genes than skin cells use. The genes that the cell doesn't need are turned off and not used. The genes that the cell is using are activated or turned on.

An abnormal change in a gene is called a mutation. The 2 types of mutations are inherited and acquired (somatic).

  • An inherited gene mutation is present in the egg or sperm that formed the child. After the egg is fertilized by the sperm, it created one cell called a zygote that then divided to create a fetus (which became a baby). Since all the cells in the body came from this first cell, this kind of mutation are in every cell in the body (including eggs or sperm) and so can be passed on to the next generation.
  • An acquired (somatic) mutation is not present in the zygote, but is acquired some time later. It occurs in one cell, and then is passed on to any new cells that are the offspring of that cell. This kind of mutation is not present in the egg or sperm, and so cannot be passed on to the next generation. Somatic mutations are much more common than inherited mutations. Most cancers are caused by acquired mutations. 

You have 2 copies of most genes – one from each parent. When someone has inherited an abnormal copy of a gene, their cells already start out with one mutation. If the other copy of the gene stops working (because of an acquired mutation, for example), the gene can stop functioning altogether. When the gene that stops working is a cancer susceptibility gene, cancer can develop. Some cancer susceptibility genes function as tumor suppressor genes. Tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (a process known as apoptosis or programmed cell death). When tumor suppressor genes don’t work properly, cells can grow out of control, which can lead to cancer. Many family cancer syndromes are caused by inherited defects of tumor suppressor genes.

Someone who isn’t born with a bad copy of a gene would have to acquire 2 different mutations for that gene not to work. Acquiring 2 mutations in the same gene takes longer than acquiring one, which is why cancers that are caused by inherited gene mutations tend to occur earlier in life than cancers of the same type that are not.

More information about gene changes that can lead to cancer can be found in  Genes and Cancer

Family cancer syndromes - when should I worry?

When many cases of cancer occur in a family, it is most often due to chance or because family members have been exposed to a common toxin, such as cigarette smoking. Less often, these cancers may be caused by an inherited gene mutation causing a family cancer syndrome. Certain things make it more likely cancers in a family are caused by a family cancer syndrome, such as

  • Many cases of an uncommon or rare type of cancer (like kidney cancer).
  • Cancers occurring at younger ages than usual (like colon cancer in a 20 year old)
  • More than one type of cancer in a single person (like a woman with both breast and ovarian cancer)
  • Cancers occurring in both of a pair of organs (both eyes, both kidneys, both breasts) 
  • More than one childhood cancer in a set of siblings (like sarcoma in both a brother and a sister)
  • Cancer occurring in the sex not usually affected (like breast cancer in a man

Before you decide that cancer runs in your family, first gather some information. For each case of cancer, look at:

  • Who is affected? How are we related?
  • What type of cancer is it? Is it rare?
  • How old was this relative when they were diagnosed?
  • Did this person get more than one type of cancer?
  • Did they smoke or have other known risk factors?

Cancer in a close relative, like a parent or sibling (brother or sister), is more cause for concern than cancer in a more distant relative. Even if the cancer was from a gene mutation, the chance of it passing on to you gets lower with more distant relatives.

It is also important to look at each side of the family separately. Having 2 relatives with cancer is more concerning if the people are related to each other (meaning that they are both on the same side of the family). For example, if both relatives are your mother's brothers it means more than if one was your father's brother and the other was your mother's brother.

The type of cancer matters, too. More than one case of the same rare cancer is more worrisome than cases of a more common cancer. For some very rare cancers, like cancer of the adrenal cortex, the risk of a certain family cancer syndrome is relatively high with even one case.

Having the same type of cancer in many relatives is more concerning than if it is several different kinds of cancer. Still, in some family cancer syndromes, a few types of cancer seem to go together. For example, breast cancer and ovarian cancer run together in families with hereditary breast and ovarian cancer syndrome (HBOC). Colon and endometrial cancers tend to go together in a syndrome called hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome.

The age of the person when the cancer was diagnosed is also important. For example, colon cancer is rare in people under 30. Having 2 or more cases in close relatives under 30 could be a sign of an inherited cancer syndrome. On the other hand, prostate cancer is very common in elderly men, so if both your father and his brother were found to have prostate cancer when they were in their 80s, it is less likely to be due to an inherited gene change.

Certain kinds of benign (not cancer) tumors and medical conditions are sometimes also part of a family cancer syndrome. For example, people with the multiple endocrine neoplasia, type II syndrome (MEN II), have a high risk of a certain kind of thyroid cancer. They also often have hyperparathyroidism (overactive parathyroid glands) and may develop adenomas (benign tumors) of the parathyroid glands and can also can get tumors in the adrenal glands called pheochromocytomas, which are usually benign.

When many relatives have the same type of cancer it is important to notice if the cancer could be related to smoking. For example, lung cancer is commonly caused by smoking, so many cases of lung cancer in a family of heavy smokers is more likely to be due to smoking than to an inherited gene change. 

Examples of family cancer syndromes

There are many family cancer syndromes, some of these are discussed briefly here as examples. For more information about a particular type of cancer and its genetic components, diagnosis, and treatment, please see that specific cancer site.

Hereditary Breast and Ovarian Cancer syndrome

For many years, doctors noticed that in some families, many of the women developed breast and or ovarian cancer. Often the cancers were found at younger than usual ages, and some of the women had more than one cancer. Some had breast cancer in both breasts, and some got both breast and ovarian cancer. Doctors studying these families coined the term Hereditary Breast and Ovarian Cancer Syndrome (HBOC).

Scientists studied the genes of these families, and discovered the genes BRCA1 and BRCA2. Because some women (and families) have HBOC based on cancer history, but don’t have mutations in these genes, scientists believe that there is at least one more gene that can cause HBOC, which they have called BRCA3. The BRCA3 gene has not yet been identified.

Mutations in either BRCA1 or BRCA2 can lead to HBOC. The risk of breast and ovarian cancer is very high with mutations in either gene, but tends to be higher with BRCA1 mutations. Along with breast and ovarian cancer, this syndrome can also lead to fallopian tube cancer, primary peritoneal cancer, male breast cancer, pancreatic cancer, prostate cancer, as well as some others. Male breast cancer, pancreatic cancer, and prostate cancer can be seen with mutations in either gene, but are more common in people with BRCA2 mutations. In the US, mutations in the BRCA genes are more common in people of Ashkenazi Jewish descent than it is in the general population.

Women with a strong family history of breast cancer and/or ovarian cancer may choose to undergo genetic counseling to estimate their risk for having a mutation in one of the BRCA genes. The genetics professional estimates the risk based on the patient’s history of cancer and the history of cancer in their family. If they have a high risk, they then can choose to be tested (more information about genetic testing can be found in  Genetic Testing for Cancer). If a mutation is present, the woman has a high risk of developing breast cancer and ovarian cancer. She can then consider steps to find cancer early and even lower her risk of getting cancer. (These are discussed in detail in  Breast Cancer and Ovarian Cancer.)

Because breast cancer is rare in men, men with this cancer are often offered genetic counseling and testing for BRCA mutations. Although having a mutation doesn’t affect a man’s future health care like it does a woman’s, it can be helpful for his relatives to know that he has a mutation and so they are at risk.

If someone in a family is found to have a BRCA mutation, it means that their close relatives (parents, siblings, and children) have a 50% chance of having a mutation, too. They may wish to be tested, or even without testing may wish to start screening for certain cancers early or take other precautions to lower their risk of cancer.

HBOC is not the only family cancer syndrome that can cause breast or ovarian cancer. For information about other genes and syndromes that raise the risk of these cancers, see  Breast Cancer and Ovarian Cancer.

Hereditary non-polyposis colorectal cancer

The most common inherited syndrome that increases a person's risk for colon cancer is called hereditary non-polyposis colorectal cancer (HNPCC), or Lynch syndrome. People with this syndrome have a high risk of colorectal cancer. Most of these cancers occur before age 50. Although the name says “non-polyposis,” people with HNPCC can get polyps, but they only have a few, not the hundreds that are seen in another syndrome that causes colon cancer called familial adenomatous polyposis.

HNPCC also leads to a high risk of endometrial cancer (cancer in the lining of the uterus) in women. Other cancers linked with HNPCC include cancer of the ovary, stomach, small intestine, pancreas, kidney, brain, ureters (tubes that carry urine from the kidneys to the bladder), and bile duct.

HNPCC can be caused a mutation in one of several genes, including MLH1, MSH2, MLH3, MSH6, PMS1, PMS, and TGFBR2. Most of these genes are involved in DNA repair.

Mutations in the genes that cause HNPCC can be found through genetic testing. Doctors and genetics professionals can look to see if HNPCC is likely based on your personal and family history using certain criteria. These, known as the Amsterdam criteria and the revised Bethesda guidelines, are discussed in detail in Colorectal Cancer .

Another option for people with colorectal or endometrial cancer is to have the tumor tissue tested for changes that can be caused when one of these genes is faulty. These changes are known as microsatellite instability (or MSI). Having normal findings (no MSI) implies that HNPCC is not present and that the genes that cause it are normal. If MSI is present, they may have HNPCC, and so are referred for genetic counseling and possible testing. For more information about genetic testing, see Understanding  Genetic Testing for Cancer).

Someone who is known to carry an HNPCC gene mutation may start screening for colorectal cancer at an early age (such as during their early 20s), or take other steps to try to prevent cancer from starting (these are discussed in more detail in  Colorectal Cancer). Women with HNPCC may start screening for endometrial cancer or take other steps to try to prevent the cancer. These are discussed in more detail in Endometrial Cancer.

If someone in a family is found to have HNPCC, it means that their close relatives (parents, siblings, and children) have a 50% chance of having a mutation, too. They may wish to be tested, or even without testing may wish to start screening for certain cancers early or take other precautions to lower their risk of cancer.

Li-Fraumeni syndrome

Li-Fraumeni syndrome is a rare syndrome that can lead to the development of a number of cancers, including sarcoma (such as osteosarcoma and soft-tissue sarcomas), leukemia, brain (central nervous system) cancers, cancer of the adrenal cortex and breast cancer. The cancers most often occur in childhood, although the breast cancers occur in young adults. People with Li-Fraumeni can also be affected by more than one cancer in their lifetime. They also seem to be at higher risk of cancer from radiation therapy, and so doctors treating these patients may try to avoid giving them radiation when possible.

This syndrome is most often caused by inherited mutations in the gene for p53 (TP53, a tumor suppressor gene). A normal gene for p53 stops the growth of abnormal cells. It can also be caused by mutations in a gene called CHEK2.

Genetic counseling and testing

People with a strong family history of cancer may want to find out about their genetic makeup. This knowledge may help the person or other family members in planning health care for the future. Since inherited mutations affect all cells of a person's body, they can often be identified by genetic testing that is done on blood samples. Genetic counseling and testing may be recommended for some people with a strong family history of cancer. For more information on genetic testing, refer to Understanding Genetic Testing for Cancer.  

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Along with the American Cancer Society, other sources of information and support include:

National Cancer Institute
Toll-free number: 1-800-4-CANCER (1-800-422-6237)

Provides accurate, up-to-date information on a variety of cancer-related topics such as finding support, financial assistance and other resources; coping with cancer; cancer genetics, etc (click the “Cancer Topics” tab on the home page). Also has an Online Cancer Genetics Services Directory to identify professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, and others). The direct link is

National Society of Genetic Counselors (NSGC)
Telephone: 1-312-321-6834

Offers a "Consumer Information" link with the following:

  • "Making Sense of Your Genes" – a 24-page guide to genetic counseling (may be downloaded and printed)
  • Directory of genetic counselors – may be searched by your area
  • "Five Questions to Ask Before Considering Genetic Testing" (may be downloaded and printed)
  • Guide on collecting family history – a helpful tool in determining possible genetic risks
  • FAQs on genetic testing and genetic counselors

*Inclusion on this list does not imply endorsement by the American Cancer Society.

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Last Medical Review: June 25, 2014 Last Revised: June 25, 2014

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