Hereditary Kidney Cancer: Part 2

Photo Credit: Urology Care Foundation

In Part 1 of this series on hereditary kidney cancer we discussed risk factors that increase the likelihood of a hereditary predisposition to kidney cancer.  In this post we outline six hereditary cancer syndromes that increase the risk to develop kidney cancer, and their features.

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 turn into cancer.  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, they have 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. Hereditary Paraganglioma type 4 (PGL4)

  • Caused by mutations in the SDHB gene (succinate dehydrogenase subunit B)
  • Individuals with this syndrome have an increased risks to develop paragangliomas and pheochromocytomas (neuroendrocrine tumors that originate from the nervous (neuro) or endocrine (hormone producing systems).
  • People with PGL4 usually inherit the condition from a parent and have a 50% chance to pass the condition to each of their children.

PGL4 and Kidney Findings:

  •  The type of kidney cancer that usually occurs in PGL4 is renal cell carcinoma (RCC).
  • If someone has PGL4, they have up to a ~14% lifetime risk of developing RCC.
  • These kidney cancers often develop at an early age. 
     

3. Tuberous Sclerosis (TS)

  • 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.

TS and Kidney Findings:

  • The type of kidney cancer that usually occurs in TS is renal cell carcinoma (RCC).
  • If someone has TS, they have up to a ~1-5% lifetime risk of developing RCC.
  • These kidney cancers often develop at an early age (average 28).
     

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, only.
  • 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:

  • The most common type of kidney cancer in indivuals with HPRC is papillary kidney cancer.
  • Kidney cancers can develop in one or both kidneys.
  • Most kidney cancers in individuals with HRPC are diagnosed before age 60 and in some cases seen as early as age 20-29.
     

5. Hereditary Leiomyomatosis Renal Cell Carcinoma (HLRCC)

  • Caused by 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). 
  • 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 ~10-30%.
  • The average age of kideny cancer diagnosis is ~36-44.
  • The most common type of kidney cancer in indivuals with HLRCC is papillary type II RCC but occasionally other types can be observed.
  • Kidney cancers in individuals with HLRCC tend to be solitary lesions, but are very aggressive and have an signficant risk of spreading, making screening and early detection very important..   

 

6. Birt-Hogg-Dubé (BHD) Syndrome

  • 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.
  • 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 a mixed oncocytic and chromophobe type.  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 ~15-30%.
  • The average age of kidney cancer diagnosis with BHD is age 50.

 

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.