Hereditary Kidney Cancer Syndromes (PDQ®)–Patient Version

Kidney cancer is a disease in which malignant (cancer) cells form in tubules of the kidney.

Kidney cancer (also called renal cell cancer) is cancer that starts in the lining of very small tubes in the kidney called renal tubules. There are two kidneys, one on each side of the backbone, above the waist. Tubules in the kidneys filter and clean the blood. They take out waste products and make urine. The urine passes from each kidney through a long tube called a ureter into the bladder. The bladder holds the urine until it passes through the urethra and leaves the body.

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Cancer that starts in the ureters or the renal pelvis (the part of the kidney that collects urine and drains it to the ureters) is called urothelial cancer. This kind of cancer is different from renal cell cancer and is not associated with the hereditary cancer syndromes described in this summary. Urothelial cancer of the renal pelvis may be associated with another hereditary condition called Lynch syndrome. To learn more, see the health professional summary on Genetics of Colorectal Cancer.

Having certain hereditary syndromes can increase the risk of kidney cancer.

Most of the time, kidney cancer risk is not passed down from parent to child. Kidney cancer that affects multiple generations of a family is called hereditary kidney cancer. Hereditary kidney cancer accounts for only 5%‒8% of all kidney cancers. It is usually linked to a hereditary cancer syndrome. A hereditary cancer syndrome is a disorder in which family members have a higher-than-average risk of developing a certain type or types of cancer. Hereditary cancer syndromes are caused by inherited, harmful genetic changes (also called pathogenic variants or mutations) in certain genes. Hereditary cancer syndromes are sometimes called inherited cancer syndromes or family cancer syndromes. People with the hereditary cancer syndromes described in this summary have an increased risk of kidney cancer.

The hereditary cancer syndromes described in this summary are:

Every person inherits two copies of each gene, one from each parent. These syndromes occur when a person inherits a mutation in one copy of the gene associated with the syndrome. This form of inheritance is called autosomal dominant inheritance.

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Hereditary and non-inherited kidney cancers differ in several ways.

This page provides information about hereditary syndromes associated with kidney cancer. It does not cover information about sporadic kidney cancer or somatic mutations found during tumor sequencing.

Genetic counseling is a communication process between a specially trained health professional and a person concerned about the genetic risk of disease.

It is not always easy to determine whether a condition in a family is inherited. Genetic counselors and other specially trained health professionals can help patients understand their personal and family medical history, their options for genetic testing, and the risks and benefits of learning genetic information. If a patient chooses to get genetic testing, it may be done using a sample of blood, saliva, or skin. Genetic test results can reveal information about other family members and can create tension in the family. Genetic counselors can help people cope with their genetic testing results, including how to discuss the results with family members.

Whether a person should get tested for hereditary kidney cancer depends on certain factors.

Certain clues in a person's medical history or family history may lead health professionals to think that an individual may have a hereditary syndrome. With kidney cancer, individuals who have one or more of the following criteria may be referred for genetic counseling and testing:

Four hereditary kidney cancer syndromes and the genes that cause them have been identified.

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)

HLRCC was considered rare, but it may be one of the most common hereditary cancer syndromes. Some people who have HLRCC may not have symptoms. HLRCC is caused by harmful changes (also called mutations or pathogenic variants) in the FH gene. People with HLRCC could have an increased risk of kidney cancer. The risk may be higher in males with FH mutations. Black people diagnosed with kidney cancer have more FH mutations than people from other racial and ethnic groups. HLRCC is associated with a unique type of kidney cancer that can be fast growing. People with HLRCC may also develop leiomyomas (benign smooth-muscle tumors) in the skin and uterus (fibroids) or paragangliomas (benign tumors near adrenal glands, blood vessels, or nerves).

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The FH gene makes a protein called fumarase. Fumarase helps cells use oxygen and produce energy. When the FH gene is mutated, cells are not able to use oxygen, which may lead to cancer. HLRCC is inherited in an autosomal dominant manner. This means that if one parent has HLRCC, there is a 50% (1 in 2) chance their child will inherit the mutation in the FH gene.

Learn more about HLRCC from the NCATS Genetic and Rare Diseases Information Center.

Von Hippel-Lindau Disease (VHL)

VHL is a rare hereditary syndrome that is caused by harmful changes (also called mutations or pathogenic variants) in the VHL gene. People with VHL have an increased risk of kidney cancer and renal cysts. VHL is associated with a clear-cell type kidney cancer, which is typically slow growing. People with VHL may also develop malignant (cancer) and benign (noncancer) tumors in many parts of the body, including the central nervous system, retina, pancreas, adrenal glands, endolymphatic sac, epididymis (in males), and broad ligament (in females).

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The VHL gene is a type of gene called tumor suppressor gene. Normally, the VHL gene prevents cells from growing and dividing too quickly. When the VHL gene is mutated in certain ways and loses its protective function, uncontrolled cell growth may lead to cancer. VHL is inherited in an autosomal dominant manner. If one parent has VHL, there is a 50% (1 in 2) chance their child will inherit the harmful genetic change in the VHL gene.

Learn more about VHL from the National Center for Advancing Translational Sciences (NCATS) Genetic and Rare Diseases Information Center.

Birt-Hogg-Dubé Syndrome (BHD)

BHD is a rare hereditary syndrome caused by harmful changes (also called mutations or pathogenic variants) in the FLCN gene. People with BHD have an increased risk of multiple types of kidney cancer that are typically slow growing. People with BHD may also develop skin tumors called fibrofolliculomas, lung cysts, and spontaneous pneumothorax (collapsed lung).

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The FLCN gene is a tumor suppressor gene. Normally, the FLCN gene prevents cells from growing and dividing too quickly. When the FLCN gene is mutated, uncontrolled cell growth may lead to cancer. BHD is inherited in an autosomal dominant manner. This means that if one parent has BHD, there is a 50% (1 in 2) chance their child will inherit the mutation in the FLCN gene.

Learn more about BHD from the NCATS Genetic and Rare Diseases Information Center.

Hereditary Papillary Renal Cancer (HPRC)

HPRC is a rare hereditary syndrome caused by harmful changes (also called mutations or pathogenic variants) in the MET gene. People with HPRC have an increased risk of a type of kidney cancer called papillary kidney cancer, which is typically slow growing. Papillary kidney cancer forms in the cells lining the very small tubes in the kidney called renal tubules.

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The MET gene makes a protein called MET that is involved in cell signaling and growth. When the MET gene is mutated, cells may not respond to signals that normally prevent them from growing, causing cancer to develop. HPRC is inherited in an autosomal dominant manner. This means that if one parent has HPRC, there is a 50% (1 in 2) chance their child will inherit the mutation in the MET gene.

Learn more about papillary kidney cancer from the NCATS Genetic and Rare Diseases Information Center.

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PDQ® Cancer Genetics Editorial Board. PDQ Hereditary Kidney Cancer Syndromes. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/kidney/patient/kidney-genetics-pdq. Accessed <MM/DD/YYYY>.

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