Kidney Cancer Genetic Testing
Introduction to Hereditary Renal Cell Cancer
Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer. Hereditary renal cell cancer (hRCC) syndromes are genetic disorders where increased risk for RCC is attributed to inherited pathogenic variants of genes. Around 5-8% of all RCCs are made up of hRCCs.
Some examples of hRCC syndromes are Von Hippel-Lindau disease, Hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and Hereditary papillary renal carcinoma. While these syndromes have their respective symptoms, general indicators of hRCC include:
- Presence of renal tumour AND any one of the following:
• Tumours are found in both kidneys (bilateral) or found in multiple locations on the kidney (multifocal)
• Early age of onset (≤46 years)
• First or second degree relative with any renal tumours
- Non-clear cell carcinoma (RCC has an unusual histology)
- A family member has a diagnosis of a hRCC syndrome
The Genetic Testing Process
Genetic testing is used to determine if an individual has the genes associated with hRCC. The process starts with a risk assessment by a doctor, genetic counselor, or other healthcare provider to determine if genetic testing is recommended. As part of this assessment, information such as family history, medical history, and lifestyle factors (diet, smoking, level of activity, etc.) are considered.
After referral for genetic testing, genetic counselling is recommended. Genetic counselling is delivered by a trained genetic counselor or health care professional experienced in cancer genetics. Topics such as the implication of test results, psychological risks and benefits, risk of passing variant to children, impact of testing for family, and other considerations are discussed. Further genetic counselling may be recommended after receiving test results.
A consent form saying that the purpose, risks, and benefits of genetic testing are understood must be signed by the individual being tested. After obtaining informed consent, a small sample of tissue or bodily fluid (usually blood) is collected and sent to a lab. Molecular genetic tests performed on the sample can search for a harmful variant of one specific gene (single-gene testing) or many harmful gene variants at once (multigene/panel testing). Additional tests to identify structural changes in chromosomes, such as missing or rearranged sections, are also sometimes performed. It may take several weeks or longer before test results are received by the genetic counselor or healthcare provider who requested the genetic testing.
A Brief Overview of Genetic Test Results
A positive result indicates that genetic variants associated with hRCC were found. People with a positive result have an increased risk for developing RCCs. For individuals who already have an RCC-diagnosis, a positive test can help confirm that the cancer was likely to an inherited genetic variant. This can help guide treatment choices along with providing information helpful to other family members (such as whether to undergo genetic testing for hRCC).
A negative result indicates that the genetic variants associated with hRCC were not found. If the person who underwent the test truly does not have genetic variants for hRCC (i.e. true negative test result), then their risk of cancer should be the same as the RCC risk in the general population.
A “benign variant” test result indicates the presence of a genetic change which is common among individuals without cancer. In other words, these genetic changes are not associated with an increase in RCC risk.
“Variants of Unknown or Uncertain significance” (VUS) is a test result reveals that a genetic change has been found, but it has not been previously associated with hRCC. A VUS result does not clarify an individual’s risk of developing RCCs. Since some gene variants may be reclassified as more information is discovered by researchers, individuals with a VUS result should remain in contact with the healthcare provider who ordered genetic testing. This ensures that the person who was tested has the most updated information on the variant found.
How to Get Started
A referral for genetic counseling is usually given by a family physician or a medical specialist (such as a urologist). For this reason, individuals interested in genetic testing should consult with these healthcare providers first.
Genetic counseling takes place in specialized locations and requires a referral. If genetic testing is recommended, the individual to be tested may be asked to go to a blood collection lab following the first appointment. Locations which offer genetic counseling include:
Cancer Risk Assessment Clinic (699 Concession Street, within the Juravinski Cancer Centre)
- Referrals can be faxed to: 905-575-6316
- For more information please visit: https://www.hamiltonhealthsciences.ca/areas-of-care/programs-and-clinics/cancer-risk-assessment-clinic/
Fred A. Litwin Family Centre (60 Murray St., 3rd floor, Room 400)
- Referrals can be faxed to: 416-619-5523
- For more information: https://www.uhn.ca/MCC/PatientsFamilies/Clinics_Tests/Genetic_Medicine_Clinic/Pages/what_expect.aspx
References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854468/
https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet
https://link-springer-com.libaccess.lib.mcmaster.ca/article/10.1007/s10897-016-0020-4
https://www.ncbi.nlm.nih.gov/books/NBK169222/
https://www.uhn.ca/MCC/PatientsFamilies/Clinics_Tests/Genetic_Medicine_Clinic/Pages/what_expect.aspx