At your next large family gathering, talking about past cancer diagnoses throughout the family tree could provide valuable insight about possible risks of inherited cancers. Researchers who study patterns of cancers within families are learning that—despite medicine’s technological advancements—a person’s family history of cancer continues to play a vital role in understanding hereditary cancers.    

While all cancers originate with some genetic change or mutation within the body, a certain percentage of these mutations are inherited. The rest occur spontaneously, and environmental factors seem to play a major role. However, even for families who share a gene variant linked to cancer, it’s important to know that having the variant does not guarantee that a person will develop cancer; it does, however, put the person at a greater risk of developing the disease.

One of the strongest indicators of inherited cancer, also called hereditary cancer syndrome, is the patient’s age at the time of diagnosis. For example, a diagnosis of colon cancer at age 35 is much stronger evidence for an inherited cancer than a diagnosis at age 85. If you know that cancer runs in your family, it’s important to schedule an appointment with your doctor so he or she can evaluate you for referral to a cancer genetics program where, along with genetic testing, they will advise on cancer preventive measures according to your risk. For example, a young person who has a gene variant associated with a greater risk of colon cancer should receive a colonoscopy much earlier than age 45, which is the age the American Cancer Society suggests.

“We know that even if you have genetic mutations that give you a high risk of cancer, environmental factors can modify that risk quite a bit,” says gastroenterologist Xavier Llor, MD, PhD, who is co-director of the Smilow Cancer Genetics and Prevention Program. “Lifestyle modifications can actually help prevent the development of that cancer. This is true more so in patients who have these mutations than in those who don’t.” As an example, Dr. Llor says, a patient who loses just 5 percent of his or her body weight can significantly reduce cancer risk.

At Yale Medicine, the team of specialists at the Smilow Cancer Genetics and Prevention Program work to provide patients accurate risk assessment, genetic testing, and access to screening and cancer preventive measures.  

Inherited cancers are those caused by a mutation in a gene that was present in the egg or sperm cell at the time of fertilization. These cancers make up a fraction of common cancers—like breast, colon, and prostate cancer—as well as less common cancers like pancreatic and ovarian cancer. It’s important to note that the presence of the mutation does not mean development of cancer is inevitable.

Below are some of the well-known genetic mutations that can be passed on to children: 

• BRCA1 or BRCA2. Women and men with BRCA1 or BRCA2 genetic mutations have a significantly higher risk of developing breast and other cancers than those without the mutations. Other cancers associated with the BRCA1 and BRCA2 genes include ovarian, pancreatic, prostate, and melanoma.
• Mutations in specific mismatch repair genes that cause Lynch syndrome. This is a hereditary disorder caused by mutations in the mismatch repair genes MLH1, MSH2, MSH6, PMS2, and EPCAM. People born with mutations in these genes have a significantly higher risk of developing colon, endometrial, and other cancers such as stomach, pancreas, urinary tract, or brain.
• CDH1. Mutations in the CDH1 gene are associated with hereditary diffuse gastric cancer, a rare type of stomach cancer, as well as breast cancer.
• PALB2. Inherited mutations in the PALB2 gene are associated with an increased risk of breast cancer. Sometimes, this mutation can also be found in families with multiple cases of pancreatic cancer.
• STK11. A mutation in the STK11 gene causes Peutz-Jeghers syndrome. People with this condition have a higher-than-average risk of developing cancers of the breast, cervix, ovary, gastrointestinal tract, and pancreas.
• PTEN. Mutations in the PTEN gene have been linked to an increased risk of breast, head and neck squamous cell carcinoma, lung, and prostate cancers.  
• CDKN2A or CDK4. Changes in the CDKN2A or CDK4 genes have been linked to an increased risk of melanoma.
• RB. Retinoblastomas are very rare cancers that develop in the eyes of children and have been linked to mutations in the RB gene.
• RET. A very specific type of thyroid cancer, called medullary carcinoma of the thyroid, is linked to germline mutations in the RET gene.  

There is a difference between familial cancers and inherited cancers. Familial cancer is used to describe a situation in which more members of a particular family are diagnosed with a type of cancer than would be statistically expected, but it’s not known why; hereditary and lifestyle causes separately or together may contribute to the high incidence in the family. In contrast, the term “inherited cancer” is used to refer to familial cancers in which a genetic cause has been identified.

The children of parents with an inherited cancer genetic mutation have a 50 percent chance of also having the mutation. If you have several family members who had cancer or some family members with cancer at a relatively young age (younger than age 50) talk to your doctor about genetic testing for yourself and your family. 

Yale Medicine cancer genetics specialists work closely together to identify possible genetic causes of cancer as early as possible. Ongoing research at Yale Cancer Center helps inform physicians of the latest treatments used to intercept cancer, such as new drugs or surgical procedures.