People inherit two copies of each gene, one from each of their parents. Hereditary cancer syndromes are typically inherited in an autosomal dominant or autosomal recessive pattern:

• Autosomal dominant. Many hereditary cancer syndromes are autosomal dominant. In this type of inheritance, inheriting a single pathogenic variant from either parent causes the hereditary cancer syndrome. In this form of inheritance, the parents, children, and siblings of a person with a hereditary cancer syndrome each have a 50% chance of having the same pathogenic variant. Both males and females are at equal risk of inheriting and passing on the pathogenic variant.
  
  In rare cases, an individual with an autosomal dominant hereditary cancer syndrome is found to have a pathogenic variant, but it was not inherited from a parent. Instead, the pathogenic variant is new and occurred randomly in that person when they were conceived. This is called a ‘de novo’ pathogenic variant. In these rare cases, parents would not be at risk of having the same pathogenic variant, so it is unlikely that siblings could share the same pathogenic variant. Each child of a person with a de novo pathogenic variant would have a 50% chance of having the same pathogenic variant.
• Autosomal recessive. Some hereditary cancer syndromes are autosomal recessive. In this type of inheritance, a person inherits two pathogenic variants—with one pathogenic variant inherited from each parent—resulting in a hereditary cancer syndrome. If both parents have a pathogenic variant, there is a 25% chance a child will inherit both copies of the pathogenic variant from each parent and have a hereditary cancer syndrome.
  
  Parents of an individual with an autosomal recessive hereditary cancer syndrome who have one pathogenic variant are known as carriers. In some cases, carriers may also have an increased risk of developing cancer. Siblings of an individual with this type of hereditary cancer syndrome have a 25% chance of having the hereditary cancer syndrome (both pathogenic variants were inherited), a 50% chance to be a carrier (meaning only one pathogenic variant was inherited), and a 25% chance of not having the hereditary cancer syndrome and also not being a carrier (meaning none of the pathogenic variants were inherited). Children of an individual with this type of hereditary cancer syndrome will be carriers of at least one pathogenic variant. Their risk of having the same hereditary cancer syndrome depends on whether their other parent also has a single pathogenic variant in the same gene.

Not all cancers that occur in multiple members of a family are caused by a hereditary cancer syndrome. In some cases, multiple people in a family may develop the same type of cancer because they share the same risk factors, such as smoking cigarettes or exposure to a toxic chemical.

However, the risk factors below suggest that someone may have a hereditary cancer syndrome:

• Having cancer at a younger age (age 50 or younger) than is typically seen in the average population
• Developing more than one cancer in:
  • the same part of the body (for instance, two colon cancers)
  • different parts of the body (for instance, breast and ovarian cancer)
  • sets of paired organs (for instance, cancer develops in both breasts, eyes, or kidneys)
• A type of cancer occurs in a person whose sex is uncommonly affected (for instance, breast cancer in males)
• Two or more first-degree relatives (parents, siblings, or children) who develop the same type of cancer, a rare type of cancer, and/or cancers known to occur in a given hereditary cancer syndrome
• Same or related types of cancers occurring in more than one generation of a family

Genetic testing looks for genes associated with hereditary cancer syndromes and may be recommended if a hereditary cancer syndrome is suspected based on someone’s personal and/or family history, or if someone has a family member with a known hereditary cancer syndrome.

Genetic testing is most often completed from a blood or saliva sample, which is then used to examine the DNA code of the genes related to a hereditary cancer risk. This testing typically looks at several genes at once and is often called “panel genetic testing.”

It’s important to note that some genes on a panel may not have been studied for as long or as well as others, or there may be more limited information about the cancer risks and recommended screening and prevention strategies for people with pathogenic variants in certain genes.

There are three types of genetic test results a person can receive:

• Positive: A positive result means a pathogenic variant was found in a hereditary cancer gene that increases the risk of developing certain cancers or tumors. Typically, gene-specific cancer screening or risk-reduction options are available for those individuals who test positive. Family members are also at risk of having the same pathogenic variant and may wish to consider their own genetic counseling and testing.
• Negative: A negative result means no pathogenic variants were found in any of the genes related to hereditary cancer. Cancer screening and risk-reducing recommendations are then based on someone’s personal and family history of cancer. Depending on family cancer history, other relatives may still benefit from their own genetic counseling and testing.
• Inconclusive (variant of uncertain significance, VUS): A variant of uncertain significance (VUS) result means a change, or variation, was found, but it is not known if this change is a pathogenic variant (associated with an increased risk of certain cancers) or a benign variant (not associated with an increased risk of cancer). Most laboratories will contact the ordering provider if they are able to reclassify the variant in the future. Most variants are later reclassified as benign (or normal gene changes). Cancer screening and risk-reducing recommendations are typically based on someone’s personal and family history of cancer. Genetic testing for the VUS in family members without a personal history of cancer is not typically recommended. However, based on the family history of cancer, genetic counseling may be recommended for other family members.

People who receive a positive result should talk to a genetic counselor or other health care provider with expertise in hereditary cancer syndromes to learn more about cancer screening recommendations, ways to reduce their risk of getting cancer, and the possible impact on cancer treatment. Those who receive a positive result should also inform their family members about the pathogenic variant, as they may be at risk of having the same pathogenic variant.

When a person is found to have a pathogenic variant causing a hereditary cancer syndrome, they have a greater than average risk of developing certain types of cancer. However, not everyone who has a hereditary cancer syndrome will develop cancer.

“The Cancer Genetics & Prevention Program at Yale/Smilow offers cutting-edge genetic testing for patients and their families, integrating standard-of-care genetic testing and research opportunities,” says Dr. Giri. “We deliver care through multiple avenues to ensure every patient who needs genetic testing can have access with informed decision-making for genetic testing. Our program offers the gold standard of genetic counseling, a new Fast-Track approach for expedited genetic testing, and point-of-care testing. We partner closely with clinical teams across the health system to meet the needs of patients, families, and health care providers to reduce the burden of cancer and promote health through genetically informed personalized care.”