How Common are Genetic Causes of Kidney Cancer?
8 Sep 2023
Kidney cancer is the 6th most common cancer in the developed world. There are many different types of kidney cancer. The most common is called clear cell kidney cancer. 75 out of 100 (75%) people with kidney cancer have clear cell kidney cancer. Other types of kidney cancer (non-clear cell kidney cancer) include papillary, chromophobe and other rarer forms.
There are several factors that can increase the risk of kidney cancer. These include smoking, obesity, high blood pressure as well as genetics. Many genetic conditions are linked with kidney cancer including Birt-Hogg-Dubé syndrome (BHD). It is thought that around 1 in 3 people with BHD will get kidney cancer. It is recommended that people with BHD get regular scans to monitor their kidneys to identify and treat any kidney cancer quickly. Other inherited kidney cancer conditions include von Hippel-Lindau (VHL) and hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC).
Genetic Causes of Kidney Cancer
For every 100 people diagnosed with kidney cancer, 3 will have another family member who has also had kidney cancer. However, mutations in genes known to increase the risk of cancer have been found in up to 16 of every 100 kidney cancer cases. This number can vary significantly based on which genes are tested.
A recently published study provided a deeper understanding of the link between genetics and kidney cancer. The researchers looked at the genetic sequence of 1336 individuals with kidney cancer in the UK 100,000 Human Genome Project. They looked at several genes that were linked to increasing the risk of cancer and how many cases of kidney cancer were linked to each gene.
They split the genes into two groups – one with genes that had been previously linked to kidney cancer and the other group with genes which had not. In total, 88 out of 1336 cases were found to have a mutation in one of the genes. 60 of these came from the group of genes previously linked to kidney cancer. 4 out of 1336 cases had a mutation in the gene folliculin (FLCN), the gene associated with BHD. There were 7 cases linked to VHL and 3 cases linked to HLRCC.
People with a mutation in a gene known to be linked with cancer tended to get kidney cancer earlier (58.6 years versus 61.5 years in those without a mutation). 19 people got kidney cancer under the age of 45. This included all 7 individuals with VHL and 2 with BHD.
Type of Kidney Cancer
912 people in the dataset had clear cell kidney cancer. Of these, 53 people had a mutation in a gene linked with cancer (5.8%). There were 224 people with non-clear cell kidney cancer in the dataset. 19 people had a mutation in a gene linked with cancer (8.5%). Genetic mutations were therefore more commonly associated with non-clear cell kidney cancer types. 2 people with BHD had chromophobe kidney cancer and 1 person had an oncocytoma. There was no information about the type of kidney cancer for the other person with BHD in this study.
Other Symptoms
None of the 4 individuals with a mutation in FLCN were reported to have any other symptoms of BHD aside from kidney cancer. This was the same for HLRCC. 4 of the 7 individuals with VHL had other symptoms of the condition.
Genetic Testing
In the UK, people who have suspected inherited kidney cancer are offered genetic testing that includes a panel of genes, including FLCN. Based on the findings of this study, the authors suggest that the panel of genes should be expanded to include other genes they found to be associated with kidney cancer.
Summary
This study found that around 6 in every 100 cases of kidney cancer had a genetic link. 4 out of 1336 people in the dataset had BHD (roughly 3 in 1000 kidney cancer cases). It was interesting that these individuals did not have any other symptoms of BHD. However, this could be due to a lack of reporting as the authors did suggest that this kind of data was not available for all participants. A central database, such as the BHD Syndrome International Registry, could be used in the future to help provide a complete picture of BHD as a condition.
Studies like these also help us better understand the link between genetics and kidney cancer. They can also help influence guidelines for kidney cancer screening and genetic testing.
