What is familial non-VHL clear cell renal cell carcinoma?

Familial non-VHL clear cell renal cell carcinoma (CCRCC) is a hereditary condition that increases the risk of the clear cell type of renal cell carcinoma (kidney cancer [2]). Currently, no other types of cancer or non-cancerous health problems are known to be associated with familial non-VHL CCRCC. The name separates this condition from von Hippel-Lindau syndrome (VHL) [3], which is the most common cause of hereditary risk for clear cell renal cell carcinoma.

What causes familial non-VHL CCRCC?

Familial non-VHL CCRCC is a genetic condition. This means that the risk of clear cell renal cell carcinoma can be passed from generation to generation in a family. A specific gene causing familial non-VHL CCRCC has not yet been discovered. Some families who appear to have familial non-VHL CCRCC have a translocation (rearrangement) involving chromosome 3. A translocation occurs when pieces of two or more chromosomes break off and reattach on another chromosome. Chromosome translocations can be passed down from generation to generation in a family. Research is ongoing to learn more about familial non-VHL CCRCC.

How is familial non-VHL CCRCC inherited?

Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. Although a specific gene has not been discovered, familial non-VHL CCRCC appears to follow an autosomal dominant inheritance pattern, in which a mutation happens in only one copy of the gene. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.

How common is familial non-VHL CCRCC?

Familial non-VHL CCRCC is considered to be very rare. The number of people and families who have familial non-VHL CCRCC is unknown.

How is familial non-VHL CCRCC diagnosed?

Familial non-VHL CCRCC is suspected when multiple family members have clear cell renal cell carcinoma, but no other symptoms of VHL [3].

What are the estimated cancer risks associated with familial non-VHL CCRCC?

The specific risk of clear cell renal cell cancer in families with familial non-VHL CCRCC is unknown.

What are the screening options for familial non-VHL CCRCC?

There are no specific screening guidelines for families suspected of having familial non-VHL CCRCC. Individuals in these families are encouraged to talk with their doctor about screening options for kidney cancer [4], including ultrasound [5] (which uses sound waves to create a picture of the internal organs), computed tomography (CT or CAT) scan [6] (which creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors), and magnetic resonance imaging (MRI) [7] (which uses magnetic fields, not x-rays, to produce detailed images of the body).

Screening options may change over time as new technologies are developed and more is learned about non-VHL CCRCC. It is important to talk with your doctor about appropriate screening tests.

Learn more about what to expect when having common tests, procedures, and scans [8].

Questions to ask the doctor

If you are concerned about your risk for kidney cancer [4], talk with your doctor. Consider asking the following questions of your doctor:

• What is my risk of developing kidney cancer?
• What can I do to reduce my risk of cancer?
• What are my options for cancer screening?

If you are concerned about your family history and think your family may have non-VHL CCRCC, consider asking the following questions:

• Does my family history increase my risk of developing kidney cancer?
• Should I meet with a genetic counselor?
• Should I consider genetic testing [9]?

Additional resources

Guide to Kidney Cancer [4]

The Genetics of Kidney Cancer [10]

What to Expect When You Meet With a Genetic Counselor [11]

National Cancer Institute
www.cancer.gov [12]

American Cancer Society
www.cancer.org [13]

CancerCare
www.cancercare.org [14]

To find a genetic counselor in your area, ask your doctor or visit the following websites:

National Society of Genetic Counselors
www.nsgc.org [15]

National Cancer Institute: Cancer Genetics Services Directory
www.cancer.gov/cancertopics/genetics/directory [16]