Hereditary Kidney Cancer Syndromes (PDQ®): Genetics - Patient Information [NCI]

What is Kidney Cancer?

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

Kidney cancer (also called renal cell cancer) 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) 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.)

What is Hereditary Kidney Cancer?

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

Most of the time, kidney cancer 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 is rare and accounts for only 5% to 8% of all kidney 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 kidney 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 kidney cancers differ in several ways.

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

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

What is Genetic Counseling and Who Should Receive It?

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

The person's family and personal medical history may be discussed, and counseling may lead to genetic testing. 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.

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. These individuals may benefit from genetic counseling and genetic testing. With kidney cancer, individuals who have one or more of the following criteria may be referred for genetic testing:

• Multiple family members have had kidney 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.

What are the Major Hereditary Kidney Cancer Syndromes?

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

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.

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 kidney 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 kidney cancer and renal cysts. VHL is associated with a clear-cell type kidney 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).

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 VHLgene. 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 kidney 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).

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 FHgene. 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).

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 FLCNgene. 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 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 METgene. 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.

What Happens After a Hereditary Kidney Cancer Syndrome Diagnosis?

Most recommendations for screening and treating people with kidney cancer are based on evidence obtained from clinical trials. Because families with these hereditary kidney cancer syndromes are rare, many of these studies did not include these types of hereditary kidney cancer. When studies of families with hereditary syndromes are not available, guidelines on how to monitor and care for patients with inherited kidney 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 Renal Cell Carcinoma 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 kidney cancer in the general population.

Are Clinical Trials Available for Hereditary Kidney Cancer Syndromes?

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:

• Kidney Cancer Home Page
• Drugs Approved for Kidney Cancer
• Genetic Testing for Inherited Cancer Susceptibility Syndromes
• Genetic and Rare Diseases Information Center
• Genetics Home Reference
• Renal Cell Cancer Treatment
• Transitional Cell Cancer of the Renal Pelvis and Ureter Treatment
• Wilms Tumor and Other Childhood Kidney Tumors Treatment

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

• About Cancer
• Staging
• Chemotherapy and You: Support for People With Cancer
• Radiation Therapy and You: Support for People With Cancer
• Coping with Cancer
• Questions to Ask Your Doctor about Cancer
• For Survivors and Caregivers

About This PDQ Summary

About PDQ

Physician Data Query (PDQ) is the National Cancer Institute's (NCI's) comprehensive cancer information database. The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries come in two versions. The health professional versions have detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions have cancer information that is accurate and up to date and most versions are also available in Spanish.

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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.

Reviewers and Updates

Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Updated") is the date of the most recent change.

The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Cancer Genetics Editorial Board.

Clinical Trial Information

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.

Clinical trials can be found online at NCI's website. For more information, call the Cancer Information Service (CIS), NCI's contact center, at 1-800-4-CANCER (1-800-422-6237).

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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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Last Revised: 2021-03-11

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