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:
- Familial melanoma and basal cell carcinoma predisposition syndromes tend to follow an autosomal dominant inheritance pattern, whereby first-degree relatives of an affected individual have a 50% chance of being affected themselves.
- Genetic susceptibility to skin cancer can be caused by variants in a single gene (monogenic variants) or variants in multiple genes giving a familial pattern (polygenic variants). Both may be identified through family history assessment, and both suggest an increased risk above general population level.
- 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! An inherited predisposition to skin cancer should be suspected if an individual is affected by multiple skin cancers, their age at diagnosis is young, there are features of a hereditary syndrome or there is a strong family history.
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.
- 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:
- 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.
Hereditary syndromes predisposing to skin cancer
The genetic conditions that predispose individuals to skin cancer are listed below.
- Familial melanoma: this is inherited in an autosomal dominant pattern and is caused by variants in the CDKN2A and CDK4 genes.
- POT1-associated tumour predisposition syndrome: this is inherited in an autosomal dominant pattern and is caused by variants in the POT1 gene.
- Variants in the PTCH1 and SUFU genes: these are inherited in an autosomal dominant pattern.
- Xeroderma pigmentosum: this is inherited in an autosomal recessive pattern and is caused by variants in the DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, POLH, XPA and XPC genes.
What do you need to do?
- Assess your patient and their family history, considering onward referral if there is a known pathogenic variant in the family or there is a red flag for an inherited cancer predisposition. Refer onward as per local and regional pathways (usually to clinical genetics services), where eligibility for genomic testing will be considered as per the National Genomic Test Directory.
- Advise the patient of the importance of sun protection, such as sun avoidance, sun-protective clothing, appropriate sunblock and the avoidance of indoor tanning.
- Advise 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.
- In patients planning a pregnancy, consider genomic counselling around risks and reproductive decisions.
- For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
- 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
- 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