Photo Credit: Urology Care Foundation
Updated: March 5, 2019
In Part 1 of this series on hereditary kidney cancer, we introduced red flags that increase the likelihood of a hereditary predisposition to kidney cancer. In this post, we review six hereditary cancer syndromes that increase the risk to develop kidney cancer.
Hereditary Cancer Syndromes that Involve the Kidney
1. von-Hippel-Lindau syndrome or VHL
- Caused by mutations in the VHL gene.
- Individuals with this syndrome have an increased risk of developing cysts and tumors throughout the body, mostly in the brain, spine, kidneys, pancreas, and eyes.
- Because of these increased risks, it is recommended that individuals with von Hippel-Lindau syndrome follow specific screening guidelines beginning as early as 1 year old.
- People with VHL usually inherit the condition from a parent and have a 50% chance to pass the condition to each of their children.
VHL and Kidney Findings:
- Most of the time, VHL-related tumors are not cancerous; however, tumors that grow on the kidneys can become cancerous. There are ways to screen for kidney tumors and cancer. If found early, these can be removed.
- The type of kidney cancer that usually occurs in VHL is renal cell carcinoma (RCC).
- If someone has VHL, he/she has a ~25-60% lifetime risk of developing RCC.
- The average age at diagnosis of RCC is 37 years; however, tumors have been detected in people with VHL as early as their late teens-20s.
2. SDHB-Related Hereditary PGL/PCC
- Hereditary Paraganglioma/Pheochromocytoma (PGL/PCC) is caused by having a mutation in one of at least 7 associated genes
- Kidney cancer can be seen in this condition, especially if someone has hereditary PGL/PCC as the result of a mutation in the SDHB gene (succinate dehydrogenase subunit B)
- Individuals with this syndrome mainly have an increased risks to develop paragangliomas and pheochromocytomas (neuroendrocrine tumors that originate from the nervous [neuro] or endocrine [hormone producing] systems).
- People with this condition usually inherit it from a parent and have a 50% chance to pass the condition to each of their children.
PGL/PCC and Kidney Findings:
- The type of kidney cancer that usually occurs in this condition is renal cell carcinoma (RCC).
- If someone has this condition, he/she has up to a ~5% lifetime risk of developing RCC.
- These kidney cancers often develop at an earlier age.
3. Tuberous Sclerosis Complex (TSC)
- Caused by mutations in the TSC1 and TSC2 genes
- Individuals with this syndrome have an increased risks to develop abnormalities of the skin, brain, kidney, and heart.
TSC and Kidney Findings:
- Five different kinds of lesions/tumors can be seen in people with TSC. Benign tumors called angiomyolipoma (70%) and cysts (20-30%) are the most common.
- While most kidney tumors in TSC are benign, renal cell carcinoma (RCC) and cancerous angiomyolipoma can occur.
- If someone has TS, they have up to a ~2-5% lifetime risk of developing RCC.
- These kidney cancers often develop at an early age (average 28-30).
4. Hereditary Papillary Renal Cell Carcinoma (HPRC)
- Caused by mutations in the MET gene
- Individuals with this syndrome have an increased risks to develop kidney cancer and benign kidney tumors. No other tumor types or other findings are known to be linked with HPRC at this time.
- People with HPRC usually inherit the condition from a parent and have a 50% chance to pass the condition to each of their children.
HPRC and Kidney Findings:
- Type 1 papillary renal cell carcinoma is the only type of kidney cancer associated with HPRC at this time.
- The lifetime risk for kidney cancer in individuals with HPRC may be as high as 90%. Kidney cancers can develop in one or both kidneys.
- The kidney cancers in individuals with HRPC are diagnosed at an average age of 42, but it has been diagnosed as early as age 19.
5. Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC)
- Caused by single mutations in the Fumarate Hydratase (FH) gene.
- Individuals with this syndrome have an increased risks to develop:
- Specific types of skin findings that may be painful, itchy, and/or sensitive to cold temperatures (cutaneous leiomyomas)
- Women with HLRCC have and increased risk to develop uterine fibroids (uterine leiomyomas).
- Kidney cancer
- People with HLRCC usually inherit the condition from a parent and have a 50% chance to pass the condition to each of their children.
HLRCC and Kidney Findings:
- The lifetime risk of kidney cancer in individuals with HLRCC is ~10-16%.
- The average age of kidney cancer diagnosis is ~44.
- The most common type of kidney cancer in individuals with HLRCC is papillary type II RCC, but other types can develop.
- Kidney cancers in individuals with HLRCC tend to be solitary lesions, but they are very aggressive and have a significant risk of spreading, making screening and early detection very important.
6. Birt-Hogg-Dubé Syndrome (BHDS)
- Caused by mutations in the FLCN (folliculin) gene.
- Individuals with this syndrome have an increased risks to develop:
- Characteristic benign skin lesions that usually occur on the face and trunk (fibrofolliculomas, trichodiscomas and acrochodons [skin tags]).
- Lung cysts and a risk for collapsed lung
- Kidney tumors/cancer
- People with BHD usually inherit the condition from a parent and have a 50% chance to pass the condition to each of their children.
BHD and Kidney Cancer:
- The most common type of kidney cancer in individuals with BHD is an oncocytic hybrid tumor that has features if both renal cell carcinoma and oncocytoma. However, other types of kidney can also be seen in individuals with BHD.
- Kidney cancers can develop in one or both kidneys.
- The lifetime risk of kidney cancer in individuals with BHD is up to ~34%.
- The median age of kidney cancer diagnosis with BHD is 48.
Kidney cancer can also be seen in other hereditary cancer syndromes. We’ve chosen to highlight six of these syndromes in this series. Please visit Part 1 of this series to view risk factors that increase the likelihood of a hereditary predisposition to kidney cancer.