Hereditary Syndromes Associated With Kidney Cancer (Renal Cell Cancer) (PDQ®)–Patient Version - National Cancer Institute

Hereditary Syndromes Associated With Kidney Cancer (Renal Cell Cancer) (PDQ®)–Patient Version

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Overview of Renal Cell Cancer

KEY POINTS

Renal cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney.
Having certain hereditary syndromes can increase the risk of renal cell cancer.
Hereditary and non-inherited renal cell cancers differ in several ways.

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

Renal cell cancer (also called kidney cancer or renal cell adenocarcinoma) is a disease in which malignant (cancer) cells are found in the lining of tubules (very small tubes) in the kidney. There are 2 kidneys, one on each side of the backbone, above the waist. Tiny 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.

Anatomy of the male urinary system (left panel) and female urinary system (right panel); two-panel drawing showing the right and left kidneys, the ureters, the bladder filled with urine, and the urethra. The inside of the left kidney shows the renal pelvis. An inset shows the renal tubules and urine. Also shown are the prostate and penis (left panel) and the uterus (right panel). — Anatomy of the male urinary system (left panel) and female urinary system (right panel) showing the kidneys, ureters, bladder, and urethra. Urine is made in the renal tubules and collects in the renal pelvis of each kidney. The urine flows from the kidneys through the ureters to the bladder. The urine is stored in the bladder until it leaves the body through the urethra.

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 different from renal cell cancer and is not associated with the hereditary syndromes described in this summary. Cancer of the renal pelvis may be associated with another hereditary condition called Lynch syndrome. (See the PDQ Health Professional summary on Genetics of Colorectal Cancer for more information.)

Having certain hereditary syndromes can increase the risk of renal cell cancer.

Most of the time, renal cell cancer is not passed down from parent to child. Renal cell cancer that affects multiple generations of a family is called hereditary renal cell cancer. Hereditary renal cell cancer is rare and accounts for only 5% to 8% of all renal cell cancers. It is usually linked to a hereditary syndrome. A hereditary syndrome is a set of signs and symptoms or conditions that occur together and is caused by certain changes in the genes that can be passed down from a parent to a child. Hereditary syndromes are sometimes called genetic syndromes or family cancer syndromes. People with the hereditary syndromes described in this summary have an increased risk of getting renal cell cancer.

The four hereditary syndromes described in this summary are:

von Hippel-Lindau disease (VHL).
Hereditary leiomyomatosis and renal cell cancer (HLRCC).
Birt-Hogg-Dubé syndrome (BHD).
Hereditary papillary renal cancer (HPRC).

Hereditary and non-inherited renal cell cancers differ in several ways.

Hereditary renal cell cancer is often diagnosed at an earlier age than sporadic renal cell cancer.
Some types of hereditary renal cell cancer can be more or less aggressive than sporadic renal cell cancer.
The treatments for hereditary renal cell cancer may differ from treatments for sporadic renal cell cancer.
People with hereditary renal cell cancer may have a higher risk of other conditions or types of cancer.

This patient summary provides information about the hereditary syndromes associated with renal cell cancer. It does not cover information about sporadic renal cell cancer or somatic mutations found during tumor sequencing.

Genetic Counseling and Testing for Hereditary Renal Cell Cancer Syndromes

KEY POINTS

Whether a person should get tested for hereditary renal cell cancer depends on certain factors.
Genetic counselors and other specially trained health professionals can help patients make an informed decision about whether to get genetic testing.

Whether a person should get tested for hereditary renal cell 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. These individuals may benefit from genetic counseling and genetic testing. With renal cell cancer, individuals who have one or more of the following criteria may be referred for genetic testing:

Multiple family members have had renal cell cancer.
Cancer developed at a young age.
Multiple tumors in one kidney or cancer in both kidneys.
Diagnosis of a type of kidney cancer that is known to be commonly inherited.

Genetic counselors and other specially trained health professionals can help patients make an informed decision about whether to get genetic testing.

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 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.

Hereditary Renal Cell Cancer Syndromes

KEY POINTS

Four hereditary renal cell cancer syndromes and the genes that cause them have been identified.
- von Hippel-Lindau disease (VHL)
- Hereditary leiomyomatosis and renal cell cancer (HLRCC)
- Birt-Hogg-Dubé syndrome (BHD)
- Hereditary papillary renal cancer (HPRC)

Mutations (changes) in several different genes can cause hereditary syndromes that increase the risk of renal cell cancer. Genes are pieces of DNA that contain information needed to define traits and genetic conditions.

Structure of DNA; drawing shows a chromosome, nucleosome, histone, gene, and nucleotide base pairs: guanine, cytosine, adenine, and thymine. Also shown is a cell and its nucleus. — Structure of DNA. Most DNA is found inside the nucleus of a cell, where it forms the chromosomes. Chromosomes have proteins called histones that bind to DNA. DNA has two strands that twist into the shape of a spiral ladder called a helix. DNA is made up of four building blocks called nucleotides: adenine (A), thymine (T), guanine (G), and cytosine (C). The nucleotides attach to each other (A with T, and G with C) to form chemical bonds called base pairs, which connect the two DNA strands. Genes are short pieces of DNA that carry specific genetic information.

Genes are passed from parents to children. For each of the hereditary syndromes described below, a child only needs to inherit a single mutated copy of a gene from one parent to have the disease. This is called autosomal dominant inheritance.

Drawing showing an autosomal dominant inheritance pattern between a father, mother, and their four children: a chromosome pair with a normal gene and a mutated gene in an affected father; two normal genes in an unaffected mother; a normal gene and a mutated gene in an affected daughter and in an affected son; and two normal genes in an unaffected daughter and in an unaffected son. — Autosomal dominant inheritance is a way a genetic trait or condition can be passed down from parent to child. One copy of a mutated (changed) gene from one parent can cause the genetic condition. A child who has a parent with the mutated gene has a 50% chance of inheriting that mutated gene. Men and women are equally likely to have these mutations and sons and daughters are equally likely to inherit them.

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

von Hippel-Lindau disease (VHL)

VHL is a hereditary syndrome that increases the risk of renal cell cancer and renal cysts. VHL is associated with a clear-cell type renal cell cancer, which is typically slow growing. People with VHL can also develop other malignant (cancer) and benign (noncancer) tumors in the central nervous system, retina, pancreas, adrenal glands, endolymphatic sac, epididymis (in males), and broad ligament (in females).

Drawing of a male figure and female figure showing areas of the body affected by von Hippel-Lindau disease. These areas include the central nervous system (including the brainstem, cerebellum, and spinal cord), retina, endolymphatic sac in the ear, adrenal glands, pancreas, kidneys, epididymis (in males), and broad ligament (in females). — Areas of the body affected by von Hippel-Lindau (VHL) disease. VHL disease is an inherited disorder that causes tumors and cysts to grow in certain areas of the body, including the central nervous system (including the brainstem, cerebellum, and spinal cord), retina, endolymphatic sac in the ear, adrenal glands, pancreas, kidneys, epididymis (in males), and broad ligament (in females). VHL disease also causes an increased risk of certain types of cancer, especially kidney cancer and pancreatic cancer.

VHL is caused by mutations in the VHL gene. 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 results that may lead to cancer. Mutated copies of the VHL gene are passed from parents to children. The syndrome caused by these mutations is inherited in an autosomal dominant fashion. If one parent has VHL, there is a 50% (1 in 2) chance for a child to inherit the mutation.

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

Hereditary leiomyomatosis and renal cell cancer (HLRCC)

HLRCC is a hereditary syndrome that increases the risk of renal cell cancer. HLRCC is associated with a unique type of kidney cancer that can be fast growing and may lead to different treatment decisions. People with HLRCC can also develop skin lesions known as leiomyomas and uterine fibroids (in females).

Drawing showing areas of the body affected by hereditary leiomyomatosis and renal cell cancer, including the skin, kidneys, and uterus. — Areas of the body affected by hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is an inherited disorder that causes an increased risk of kidney cancer. It can also cause lesions in the skin and uterus (in females).

HLRCC is caused by mutations in the FH gene. 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. These mutations are passed from parents to children. The syndrome caused by these mutations is inherited in an autosomal dominant fashion. If one parent has HLRCC, there is a 50% (1 in 2) chance for a child to inherit the mutation.

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

Birt-Hogg-Dubé syndrome (BHD)

BHD is a hereditary syndrome that increases the risk of multiple types of kidney cancer that are typically slow growing. People with BHD can also develop skin lesions known as fibrofolliculomas, lung cysts, and spontaneous pneumothorax (collapsed lung).

Drawing showing areas of the body affected by Birt-Hogg-Dube syndrome, including the skin, lungs, and kidneys. — Areas of the body affected by Birt-Hogg-Dube (BHD) syndrome. BHD syndrome is an inherited disorder that causes an increased risk of kidney cancer, benign (not cancer) skin lesions, collapsed lungs, and lung cysts.

BHD is caused by mutations in the FLCN gene. 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 result that leads to cancer. Mutated copies of the FLCN gene are passed from parents to children. The syndrome caused by these mutations is inherited in an autosomal dominant fashion. If one parent has BHD, there is a 50% (1 in 2) chance for a child to inherit the mutation.

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

Hereditary papillary renal cancer (HPRC)

HPRC is a hereditary syndrome that increases the risk of a type of kidney cancer known as papillary type 1 kidney cancer, which is typically slow growing. Papillary kidney cancer forms in the cells lining the renal tubules.

Papillary renal cancer; drawing showing the left kidney, renal pelvis, and ureter. Also shown is a pullout of the renal tubules, which is where urine is made. — Papillary renal cancer forms in cells that line the renal tubules in the kidney. The renal tubules remove waste from the blood and make urine. Urine moves through the renal tubules into the renal pelvis and ureter, which carries urine from the kidney to the bladder.

HPRC is caused by mutations in the MET gene. 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. Mutations in the MET gene are passed from parents to children. The syndrome caused by these mutations is inherited in an autosomal dominant fashion. If one parent has HPRC, there is a 50% (1 in 2) chance for a child to inherit the mutation.

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

Follow-up Care After a Hereditary Renal Cell Cancer Syndrome Diagnosis

Most recommendations for screening and treating people with renal cell cancer are based on evidence obtained from clinical trials. Because families with these hereditary renal cell cancer syndromes are rare, many of these studies did not include these types of hereditary renal cell cancer. When studies of families with hereditary syndromes are not available, guidelines on how to monitor and care for patients with inherited renal cell cancer are based on the expert opinion and consensus of healthcare professionals who have experience in treating families with these syndromes.

Families with these hereditary syndromes are watched closely for signs of disease in the kidneys and in other organs. Most kidney tumors that occur can be removed by surgery, but they may recur (come back). Other treatment options may be available.

See the PDQ Health Professional summary on the Genetics of Kidney Cancer (Renal Cell Cancer) for information about screening and treatment options for each of the hereditary syndromes described in this summary. See the PDQ summary on Renal Cell Cancer Treatment for information about the treatment of renal cell cancer in the general population.

Current Clinical Trials

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

To Learn More About Kidney (Renal Cell) Cancer

For more information from the National Cancer Institute and the National Institutes of Health about kidney cancer and genetics, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:

About This PDQ Summary

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Purpose of This Summary

This PDQ cancer information summary has current information about the genetics of kidney cancer. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.

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A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

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PDQ® Cancer Genetics Editorial Board. PDQ Hereditary Syndromes Associated With Kidney Cancer (Renal Cell Cancer). 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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