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 3%–5% of renal cancer is thought to be associated with inherited cancer predisposition syndromes; it is important to use family history to identify those at increased risk who may be eligible for genomic testing and surveillance.
- If an individual is found to carry a gene variant that diagnoses an inherited cancer predisposition syndrome, they are at high risk of renal cancer and may be at increased risk of other cancers too.
- Inherited renal cancer syndromes often follow autosomal dominant inheritance: first-degree relatives have a 50% chance of carrying the familial gene variant responsible.
- Alert! Renal cancers occurring as a result of an inherited renal cancer predisposition syndrome are more likely to appear at a younger age (below 50 years old), cause multiple cancers and affect both kidneys.
Example clinical scenario
A 24-year-old man comes to see you worried about his family history of renal cancer. His grandfather died of renal 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
- A proportion of familial renal cancer is caused by multifactorial and polygenic inheritance: inheriting multiple lower-risk genetic variants that collectively increase cancer risk and interact with environmental risk.
- A small proportion of familial renal cancer is caused by inherited high-risk pathogenic variants in cancer predisposition genes such as VHL.
- Flags for an above-population risk include:
- a diagnosis of renal cancer under the age of 50 (personal or family history);
- bilateral or multifocal renal cancer, regardless of age; and
- the presence of features of an inherited cancer predisposition 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).
- 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
Examples of renal cancer predisposition syndromes with their associated features:
- Von Hippel-Lindau disease (VHL gene).
- Cowden Syndrome: skin lesions, risk of thyroid and endometrial cancer (PTEN gene).
- Lynch syndrome: transitional cell carcinoma of the renal pelvis, bowel cancer (multiple).
- Birt-Hogg-Dubé syndrome: lung cysts and pneumothorax.
- Hereditary leiomyomatosis (uterine and skin) and renal cell carcinoma (FH gene).
- BAP1-associated tumour predisposition syndrome; uveal melanoma, mesothelioma (BAP1 gene).
What do you need to do?
- Take an accurate family history. Focus on the age of any cancer diagnosis in relatives, the sites of tumours and associated features, presence of multiple cancers (including bilateral or multi-focal renal cancer).
- Refer to clinical genetics. Ideally advise referral of the affected relative in the first instance, if any of the following is present in the personal family history:
- a diagnosis of renal cancer under the age of 50 (personal or family history);
- bilateral or multifocal renal cancer, regardless of age;
- the presence of features of an inherited cancer predisposition 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).
- Management in primary care should include:
- advising the patient about suspicious symptoms to be aware of, including haematuria;
- addressing lifestyle factors such as smoking and alcohol consumption;
- managing patient anxiety;
- advising the patient to return if their family history changes; and
- providing information regarding national screening programmes such as breast, bowel and cervical screening programmes.
- 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 renal 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
- National Cancer Institute: Genetics of renal cell carcinoma (health professional version)
- NHS England: National Genomic Test Directory
- NHS England Genomics Education Programme: Von Hippel-Lindau disease
For patients
-
- Macmillan Cancer Support: Causes and risk factors of kidney cancer
- National Cancer Institute: Genetics of renal cell carcinoma (patient version)
- NHS Health A to Z: Kidney cancer