Presentation: Patient with a family history of renal cancer
Inherited cancer predisposition is thought to account for around 5% of kidney cancers and often occurs in younger people. Risk can be identified in several different ways, including through family history assessment.
At a glance:
- Around 5% of kidney cancer is thought to be associated with inherited cancer predisposition syndromes.
- Genetic susceptibility to kidney cancer can be caused by variants in a single gene (monogenic variants) or in multiple genes (polygenic variants). Both types may be identified through family history assessment.
- Hereditary renal cancer syndromes are often autosomal dominant: first-degree relatives of an affected individual have a 50% chance of being affected themselves.
- Alert! Kidney cancers occurring as a result of an inherited kidney cancer predisposition syndrome are more likely to appear at a younger age (below 50 years old), cause multiple tumours and affect both kidneys.
Example clinical scenario
A 24-year-old man comes to see you worried about his family history of kidney cancer. His grandfather died of kidney cancer when he was younger, and his mother has recently been diagnosed with it at the age of 48.
Identifying those at risk of a genetic condition
- Flags for an increased risk above the general population, including underlying genetic diagnosis, include:
- a diagnosis of kidney cancer under the age of 50;
- bilateral or multifocal renal cancer, regardless of age; and
- the presence of features of an inherited cancer syndrome, including cerebellar or spinal haemangioblastoma, retinal angioma, uveal melanoma, phaeochromocytoma or paraganglioma, mesothelioma spontaneous pneumothorax, cutaneous leiomyomata or uterine leiomyomas (in a patient under 40 years of age with a pathology suggesting an FH mutation).
- The family may already have a diagnosis of an inherited cancer predisposition syndrome, and/or there may already be a known pathogenic variant in the family.
Hereditary syndromes predisposing to renal cancer
The genetic conditions that predispose individuals to renal cancer are listed below. All are inherited in an autosomal dominant pattern.
- Von Hippel-Lindau disease, caused by variants in the VHL gene.
- Hereditary papillary renal cell carcinoma, caused by variants in the MET gene.
- Birt-Hogg-Dubé syndrome, caused by variants in the FLCN gene.
- Hereditary leiomyomatosis and renal cell carcinoma, caused by variants in the FH gene.
- BAP1 tumour predisposition syndrome, caused by variants in the BAP1 gene.
What do you need to do?
- Assess the patient and their family history, and consider onward referral if there is a known pathogenic variant in the family or a red flag for an inherited cancer predisposition. Refer onward along local or regional pathways (usually clinical genetics), where eligibility for genomic testing will be considered.
- Consider and advise the patient regarding modifiable risk factors such as smoking, hypertension, a healthy BMI and a healthy, balanced diet. This applies to all risk categories, including near-population risk.
- Advise the patient about symptoms that would warrant urgent referral, such as haematuria.
- Following referral and assessment, recommendations may be made regarding surveillance.
- If your patient is planning a pregnancy and has a diagnosis of an inherited form of kidney cancer, discuss the risk of their child inheriting the condition and consider referring them for genomic counselling about their reproductive options.
- 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
- Genomics Education Programme: Von Hippel-Lindau disease
- National Cancer Institute: Genetics of renal cell carcinoma (health professional version)
- NHS England: National Genomic Test Directory
For patients
- National Cancer Institute: Genetics of renal cell carcinoma (patient version)
- NHS Health A to Z: Kidney cancer
- Macmillan Cancer Support: Causes and risk factors of kidney cancer