Hereditary Cancer: What Your Family History Can Tell You About Your Risk

When several people in the same family develop cancer, it is natural to wonder whether genetics is responsible. But having relatives with cancer does not necessarily mean a person has inherited a cancer-causing genetic change.

Most cancers are not hereditary. Still, inherited genetic changes can substantially increase the risk of certain cancers, sometimes leading doctors to recommend earlier or more frequent screening, genetic testing or preventive measures.

“Most cancers are not caused by an inherited genetic predisposition,” explains Arelis Mártir-Negrón, M.D., FAMG, medical geneticist at Baptist Health Herbert Wertheim Cancer Institute. “Approximately 5–10 percent of cancers are traditionally considered hereditary, although more recent data suggest that this may be closer to 10–15 percent.”

Understanding the difference between hereditary cancer and simply having cancer in the family can help people determine when their family history deserves a closer look.

What Makes a Cancer Hereditary?

Cancer develops when genetic changes allow cells to grow and divide abnormally. Most of these changes accumulate during a person's lifetime and are not passed from parent to child.

Hereditary cancer is different. It occurs when someone is born with a harmful change, or variant, in a gene associated with an increased risk of cancer. That variant can potentially be passed to the person's children.

Importantly, inheriting such a variant does not mean cancer is inevitable.

“If an individual is born with a harmful genetic variant, it does not mean they are guaranteed to develop all the associated cancers,” Dr. Mártir-Negrón says. “What it does mean is that the individual has a statistically and significantly higher risk for certain cancer types compared to someone in the general population.”

The amount of additional risk varies considerably depending on the gene.

For example, Dr. Mártir-Negrón says a harmful variant in BRCA2 can increase a woman's lifetime breast cancer risk to approximately 69 percent, compared with about 13 percent in the general population. BRCA1 and BRCA2 are genes that normally help repair damaged DNA. Certain inherited changes in these genes can interfere with that protective function.

Other genetic conditions can affect different cancers. Lynch syndrome, for example, is an inherited condition associated with colorectal cancer as well as several other cancers. While the average person's lifetime risk of colorectal cancer is about 4 percent, Dr. Mártir-Negrón says the risk with Lynch syndrome can range from approximately 20 to 75 percent, depending on the gene involved.

Some Cancers Have Stronger Hereditary Links

Breast cancer and the BRCA genes are perhaps the best-known examples of hereditary cancer, but they are far from the only ones.

“Ovarian and pancreatic cancers have some of the strongest associations with hereditary genetic predisposition, with harmful genetic variants identified in approximately 25 percent and 15 percent of cases respectively,” Dr. Mártir-Negrón says.

Genetic testing is therefore recommended for people diagnosed with these cancers, as well as certain close relatives with particular cancers, she says.

Breast, colorectal and uterine cancers can also be associated with inherited genetic changes. And cancer genetics has expanded considerably beyond BRCA1 and BRCA2.

“We now know of several other genes apart from BRCA1 and BRCA2 where harmful genetic variants can increase cancer risk and impact medical management,” Dr. Mártir-Negrón says.

For that reason, genetic testing today may use a multigene panel, which analyzes many genes associated with hereditary cancer at the same time rather than looking for changes in only one or two genes.

Why Age and Family Relationships Matter

Simply counting how many relatives have had cancer does not provide a complete picture of hereditary risk. The type of cancer, the relatives affected and their ages when diagnosed can all provide important clues.

“Many cancers diagnosed at a younger age, particularly before age 50, can raise suspicion for a hereditary predisposition and may warrant genetic testing,” Dr. Mártir-Negrón says. “Some cancers, such as ovarian cancer, warrant genetic testing regardless of the age at diagnosis.”

Doctors also pay particular attention to first-degree relatives — a person's parents, siblings and children — when assessing family history.

Other patterns can also be important, including multiple relatives with the same or related cancers, an individual who develops more than one type of cancer, or a cancer that is uncommon for a person's sex. Family history can affect screening recommendations even when genetic testing does not find a harmful variant.

“Depending on the cancer and the individual's calculated risk, screening may need to begin 5–10 years earlier than the standard recommendation for the general population,” Dr. Mártir-Negrón says.

Why Cancer Can Seem to ‘Skip’ a Generation

Families sometimes assume a hereditary cancer condition skipped a generation because a grandparent and grandchild developed cancer while the parent in between did not. Genetically, however, that may not be what happened.

A person can inherit a cancer-predisposition variant without ever developing the associated cancer. That person can still pass the variant to a child.

“These types of genetic variants don’t skip over generations; they just impact different individuals in different ways,” Dr. Mártir-Negrón says.

This concept is one reason a detailed family history can be valuable even when some relatives carrying a genetic variant remained healthy.

Family History Is About More Than Genes

Cancer occurring repeatedly within a family is not always caused by an inherited mutation. Families frequently share behaviors and environmental exposures that can also influence risk.

“Family members often share not only genes, but also lifestyle habits and environmental exposures, which can influence cancer risk,” Dr. Mártir-Negrón says.

Smoking, for example, increases the risk of lung and several other cancers, while secondhand smoke increases lung cancer risk. Alcohol consumption is associated with increased breast cancer risk, while obesity and unhealthy dietary patterns can contribute to several cancers.

Families may also share exposure to substances in their homes, workplaces or communities. Radon is associated with lung cancer, while asbestos exposure is strongly associated with mesothelioma, a cancer affecting the thin tissue that lines certain organs, most commonly the lungs.

This means a strong family history deserves careful assessment rather than an assumption that genes are necessarily responsible.

When to Consider Genetic Counseling and Testing

People concerned about cancer in their family can start by collecting information. Ideally, that includes which relatives developed cancer, the specific type of cancer and their age at diagnosis.

“If cancer runs in your family, consider making an appointment with a genetic counselor or other genetics professional,” Dr. Mártir-Negrón says.

A genetics professional can review the pattern of cancers in the family and determine whether genetic testing is appropriate. If testing is recommended, the results can sometimes directly influence medical care.

“If an actionable genetic mutation is identified, it may change your medical management, including cancer screening and, in some cases, preventive treatment or surgery,” she says.

An actionable mutation is a genetic finding for which established medical steps can be taken to reduce risk, detect cancer earlier or otherwise guide care.

A negative genetic test, however, does not automatically mean someone has average cancer risk.“Even if genetic testing is negative, a formal cancer-risk assessment based on your family history may identify an increased risk and lead to different screening recommendations,” Dr. Mártir-Negrón says.

For example, someone with a first-degree relative who developed colorectal cancer may be advised to begin colonoscopy at age 40 or five to 10 years before the relative's age at diagnosis. Screening may also be performed more frequently than the standard interval for people at average risk.

Genetic Testing Continues to Evolve

Genetic testing has become more comprehensive, accessible and, in many cases, less expensive. At the same time, researchers continue to identify additional genes associated with cancer.

That can make older genetic test results worth revisiting. A test that was considered comprehensive years ago, in other words, may not have examined all the genes included in today's panels.

“If you had genetic testing several years ago, it may also be worth discussing the results with a genetics professional,” Dr. Mártir-Negrón says. “Genetic testing technology and the number of genes included in testing panels have expanded over time.”