Presentation: Patient with a family history of cancer
Around 5%–10% of cancers are caused by pathogenic variants in a cancer susceptibility gene. The inheritance of multiple lower-risk variants also increases cancer risk. Identifying individuals who are at increased risk can enable targeted screening, prevention and early diagnosis.
At a glance:
- Around 5%–10% of cancers are caused by a constitutional (germline) pathogenic variant in a single cancer susceptibility gene (this is known as a monogenic condition).
- The inheritance of multiple lower-risk variants (polygenic inheritance) also increases an individual’s risk of cancer.
- Identifying individuals at an increased risk of cancer can enable targeted screening, prevention and early diagnosis.
- Alert! Hereditary cancers may be diagnosed at an unusually early age, may occur bilaterally and/or more than once, and may be present in one or more family members.
Example clinical scenario
A 40-year-old woman presents with concerns about her family history of cancer. She reports multiple diagnoses of cancer in her family, and she is now worried that there may be an underlying genetic susceptibility.
Identifying those at risk of a genetic condition
- Individuals without a significant family history of cancer can be screened out using the highly sensitive screening questions in table 1. These questions are designed to flag individuals with either a monogenic or polygenic susceptibility to cancer. If they answer yes to any of these questions, a more detailed family history should be taken.
- Flags for an underlying genetic diagnosis include:
- cancers occurring at an unusually young age (for example, breast cancer diagnosed in women at or before the age of 40);
- a cancer occurring in a gender in which it does not commonly occur (for example, male breast cancer);
- the absence of typical associated environmental factors;
- a strong history of the cancer or associated cancers in genetically related individuals (for example, breast and ovarian cancer);
- a presentation that is more severe than usual; and
- bilaterally affected organs (for example, bilateral breast cancer).
Table 1: Screening questions for hereditary cancer
| 1. Have you ever been diagnosed with cancer, a non-cancerous tumour or bowel polyps? | Yes/No |
| 2. Do you have a relative who has been diagnosed with breast cancer under the age of 40 or a male relative with breast cancer? | Yes/No |
| 3. Do you have a relative who has been diagnosed with breast cancer in both breasts (bilateral breast cancer) or twice in the same breast more than five years apart? | Yes/No |
| 4. Do you have a relative who has been diagnosed with ovarian cancer? | Yes/No |
| 5. Do you have two or more relatives on the same side of the family who have developed breast cancer and/or ovarian cancer? | Yes/No |
| 6. Have your parents, children or siblings been diagnosed with cancer under the age of 50? | Yes/No |
| 7. Have your parents, children or siblings been diagnosed with cancer twice under the age of 70? | Yes/No |
| 8. Do you have two or more relatives on the same side of the family who have developed the same type of cancer, tumour or bowel polyps? | Yes/No |
| 9. Do you have three or more relatives on the same side of the family who have developed the same type of cancer, tumour or bowel polyps? | Yes/No |
| 10. Have your parents, children or full siblings developed one of the cancers or tumours from this list*?
*Bladder cancer, bowel cancer, breast cancer, gastrointestinal stromal tumour, glioblastoma, kidney cancer, melanoma, mesothelioma, ovarian cancer, pancreatic cancer, paraganglioma, phaeochromocytoma, pituitary tumour, prostate cancer, sarcoma, stomach cancer, urinary tract cancer, womb cancer |
Yes/No |
Adapted using NICE familial breast cancer above-population risk criteria, British Society of Gastroenterology guidelines for hereditary colorectal cancer and testing criteria from the National Genomic Test Directory
What do you need to do?
- Use the screening questions (table 1) to determine whether there could be a significant family history of cancer. If the individual answers yes to any of the questions, refer to the National Genomic Test Directory to determine the patient’s eligibility for further testing or additional screening investigations.
- Individuals with a suspected monogenic or polygenic susceptibility to cancer should be referred to their local clinical genetics service for further discussion regarding the suitability of genomic testing.
- Make it clear to individuals that if additional members of their family are diagnosed with cancer, their own estimated cancer risk may change. For example, if an individual’s family history of cancer is significant enough to qualify them for extra screening but not genomic testing, having more relatives diagnosed with cancer may push them over the threshold and qualify them for testing.
- Use the opportunity to discuss modifiable risk factors for cancer development, such as smoking, obesity and diet.
- Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.
Resources
For clinicians
- Gen-e Up (Genetics Education for Primary Care): Red flags summary
- NHS England: National Genomic Test Directory
For patients
- Cancer Research UK: Family history and inherited cancer genes
- National Cancer Institute: The genetics of cancer
- NHS Health A to Z: Predictive genetic tests for cancer risk genes