Presentation: Patient with a family history of skin cancer
Genetic susceptibility to skin cancer can be caused by variants in single or multiple genes. Family history and the clinical presentation of any existing cancers may indicate an inherited predisposition.
At a glance:
- A family history of multiple melanoma or basal cell carcinoma at younger ages, or a family history of an inherited cancer predisposition syndrome may indicate that a patient is at above-population risk of developing these.
- Genetic susceptibility to skin cancer can be caused by variants in a single gene (inherited cancer predisposition syndrome) or variants in multiple genes giving a familial pattern (polygenic variants).
- Apparent clustering of skin cancers in a family may represent shared environmental risk factors, with risk also depending on skin type and sun exposure.
- Clinicians should advise the patient of the importance of sun protection, including sun avoidance, sun-protective clothing, appropriate sunblock and the avoidance of indoor tanning.
- Alert! Although cancer is common in the general population, inherited cancer predisposition syndromes account for just 5% of all cancers.
Example clinical scenario
A 16-year-old boy, accompanied by his mother, presents with concerns about his family history of skin cancer. His estranged father had multiple skin cancers that required treatment.
Identifying those at risk of a genetic condition
- Less than 1% of basal cell carcinomas and squamous cell carcinomas are linked to a hereditary predisposition syndrome.
- These include familial melanoma syndromes (CDKN2A and CDK4 genes), familial nevoid basal carcinoma or Gorlin syndrome (PTCH1 and SUFU genes) and xeroderma pigmentosa
- Families may already have a diagnosis of an inherited cancer predisposition syndrome, or there may already be a known pathogenic variant within the family.
- You should suspect an inherited predisposition to melanoma in individuals with a personal history of:
- one melanoma or more under the age of 18;
- two melanomas under the age of 30;
- three melanomas at any age; and
- melanoma or atypical moles and a family history of melanoma, atypical moles or pancreatic cancer.
- An inherited predisposition to basal cell carcinomas should be suspected in individuals with more than five basal cell carcinomas under the age of 50.
- The following are associated features of either melanoma or basal cell carcinomas:
- malignant mesothelioma (lung or peritoneal);
- renal cell carcinoma;
- meningioma; and
- cholangiocarcinoma or hepatocellular carcinoma.
What do you need to do?
- Assess your patient and their family history, focussing on whether there is a known pathogenic variant in the family, age of cancer diagnosis in relatives, presence of multiple cancers and skin cancer type.
- Refer to clinical genetics if there is a known pathogenic variant or inherited cancer predisposition syndrome in the family.
- If not, advise referral of a relative affected with skin cancer in the first instance, if any of the following is present in the family history:
- one melanoma (or more) under the age of 18;
- two melanomas under the age of 30;
- three melanomas at any age; and
- melanoma or atypical moles and a family history of melanoma, atypical moles or pancreatic cancer
- associated cancers: uveal melanoma, malignant mesothelioma (lung or peritoneal), renal cell carcinoma, meningioma, cholangiocarcinoma or hepatocellular carcinoma.
- Management in primary care should include:
- advising the patient of the importance of regular self-examination for any changes to moles or skin lumps (such as change in size, colour, itching, bleeding and/or non-healing), which should prompt an urgent review;
- advising the patient of the importance of sun protection, such as sun avoidance, sun-protective clothing, appropriate sunblock and the avoidance of indoor tanning;
- managing patient anxiety; and
- advising the patient to return if their family history changes.
Resources
For clinicians
- National Cancer Institute: Genetics of skin cancer (health professional version)
- NHS England: National Genomic Test Directory
- Orphanet: Familial melanoma
For patients
- Cancer Research UK: Risks and causes of skin cancer
- Macmillan Cancer Support: Causes and risk factors of melanoma