What are genes?

Genes carry individual collections of information within each cell of the human body. Each gene is made of a unique sequence of DNA. Researchers working on the Human Genome Project have estimated that there are as many as 30,000 different genes in each cell. Genes are packaged onto chromosomes. There are 23 pairs of chromosomes in each cell. One chromosome of each pair is inherited from the person's father and one from the person's mother.

Genes control how a cell functions, including how quickly it grows, how often it divides, and how long it lives. To control these functions, genes produce proteins that perform specific tasks and act as messengers for the cell. Therefore, it is essential that each gene have the correct instructions or "code" for making its protein so that the protein can perform the proper function for the cell.

What role do genes play in kidney cancer?

Cancer begins when one or more genes in a cell are mutated (changed), creating an abnormal protein or no protein at all. The information provided by an abnormal protein is different from that of a normal protein, which can cause cells to multiply uncontrollably and become cancerous.

A person may either be born with a genetic mutation in all of their cells (germline mutation) or acquire a genetic mutation in a single cell during his or her lifetime. An acquired mutation is passed on to all cells that develop from that single cell (called a somatic mutation). Most kidney cancers (about 95%) are considered sporadic, meaning that the damage to the genes occurs by chance after a person is born. Inherited kidney cancers are less common (about 5%) and occur when gene mutations are passed within a family, from one generation to the next. Kidney cancer may also be called renal cell carcinoma.

What are the chances a mutated gene is inherited?

Every cell usually has two copies of each gene: one inherited from a person’s mother and one inherited from a person’s father. Hereditary kidney cancer usually follows an autosomal dominant inheritance pattern, in which a mutation needs to happen in only one copy of the gene for the person to have an increased risk of getting the disease. This means that a parent with a gene mutation may pass on a copy of the normal gene or a copy of the gene with a 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 gene mutation also has a 50% chance of having the same mutation.

What is a person's average risk for kidney cancer?

A person at average risk for kidney cancer has less than a 1% chance of developing kidney cancer during his or her lifetime.

How common is kidney cancer?

Kidney cancer is the seventh most common cancer and the tenth most common cause of cancer death in men. It is the ninth most common cause of cancer in women. In 2008, an estimated 54,390 adults (33,130 men and 21,260 women) in the United States will be diagnosed with kidney cancer. It is estimated that 13,010 deaths (8,100 men and 4,910 women) from this disease will occur this year.

How can a person know if he or she has inherited a genetic mutation that increases his or her risk of kidney cancer?

Only genetic testing can determine whether a person has a genetic mutation. Most experts strongly recommend that people considering genetic testing first consult a genetic counselor. Genetic counselors are trained to explain the risks and benefits of genetic testing.

For more information, read Cancer.Net: Genetic Testing and Cancer.Net: What to Expect When Meeting With a Genetic Counselor.

How does a person know if kidney cancer runs in the family?

If a person’s first-degree relatives (parents, brothers, sisters, children) have had kidney cancer, or if there are many cases in the family (including grandparents, aunts, uncles, nieces, nephews, grandchildren, cousins), there may be a chance that kidney cancer runs in the family. This is especially true when family members have been diagnosed with kidney cancer before the age of 50, had cancer in both kidneys, and/or had multiple tumors in the same kidney.

What is a person's risk if kidney cancer runs in the family?

A person has an increased risk of kidney cancer if their first-degree relatives developed kidney cancer before age 50. Identifying a specific genetic condition in the family can help determine the risk of other family members developing kidney cancer.

Which inherited genetic mutations raise the risk of kidney cancer?

There are a growing number of genes thought to be associated with an increased risk of kidney cancer. Some of the most common genetic conditions that increase the risk of kidney cancer are described below. Most conditions are associated with a specific type of kidney cancer. Identifying a specific genetic syndrome in a family can help individuals and their doctors develop an appropriate cancer screening plan and, in some cases, help to determine the best treatment. Some genetic conditions also increase a person’s risk for noncancer-related health problems for which screening and early detection may be beneficial.

Von Hippel-Lindau syndrome (VHL). People with VHL have an increased risk of developing several types of tumors. Most of these tumors are benign (noncancerous). However, people with VHL have about a 40% risk of developing kidney cancer. The specific type of kidney cancer associated with VHL is called clear cell kidney cancer. Other parts of the body where tumors can develop include the eye (retinal angioma), brain and spinal cord (hemangioblastoma), adrenal glands (pheochromocytoma), and ear (endolymphatic sac tumor). Tumors of the ear may lead to partial or complete hearing loss. People with VHL can also develop a cyst on their kidneys and pancreas, or on a man’s testicles (epididymal cystadenomas). Symptoms of VHL usually develop in a person’s 20s or 30s, but can begin in childhood. Approximately 20% of people with VHL have no family history of the condition.

The gene associated with VHL is also called VHL. The VHL gene is called a tumor suppressor gene. A tumor suppressor gene makes proteins that prevent tumor formation by limiting cell growth. Mutations in a tumor suppressor gene results in a loss of the ability to restrict tumor growth and, as a result, cancer can develop. Genetic testing for VHL is available, and it is recommended that a person consult a doctor or a genetic counselor for more information based on his or her individual medical profile. Genetic testing is often recommended for anyone who may have VHL and for any family members, children or adults, at risk for VHL.

Screening for symptoms of VHL should begin early in families at risk and include:

• Yearly eye examination to look for retinal tumors, beginning around age 2
  
  
• Yearly physical examination
  
  
• Yearly 24-hour urine test to screen for elevated catecholamines (a chemical produced by the body that may be at higher levels for people with VHL), beginning around age 2
  
  
• Yearly abdominal ultrasound (the use of sound waves to create a picture of the internal organs) to look at the kidneys, pancreas, and adrenal glands beginning in the teenage years; change screening to abdominal computed tomography (CT or CAT) scan in adulthood
  
  
• Magnetic resonance imaging (MRI) of the brain and spine every two years beginning in the teenage years

For more information, read the Cancer.Net Guide to Von-Hippel-Lindau Syndrome.

Hereditary non-VHL clear cell renal cell carcinoma. Hereditary non-VHL clear cell renal cell carcinoma is a genetic condition that increases a person’s risk of developing clear cell renal cell carcinoma (CCRCC). A family may have hereditary non-VHL CCRCC if multiple family members have been diagnosed with CCRCC.

A specific gene that causes non-VHL CCRCC has not been discovered. Some families who have hereditary non-VHL CCRCC may have a specific rearrangement of chromosome 3. In other families, the genetic change responsible for the increased risk of kidney cancer is unknown. Genetic testing is available to look for the specific chromosome 3 rearrangement. Yearly screening for kidney cancer with ultrasound, MRI, and CT scan beginning at age 20 has been suggested for families with this rare condition.

For more information, read the Cancer.Net Guide to Hereditary Non-von-Hippel-Lindau Clear Cell Renal Cell Carcinoma.

Hereditary papillary renal cell carcinoma (HPRCC). HPRCC is a genetic condition that increases the risk of type 1 papillary renal cell carcinoma. People who have HPRCC have an increased risk of multiple kidney tumors and an increased risk of developing tumors on both kidneys.

HPRCC is suspected when two or more close relatives have been diagnosed with type 1 papillary renal cell carcinoma. In these families, people are typically diagnosed with HPRCC while in their 40s (or sometimes at an older age). People with HPRCC may develop multiple kidney tumors in one or both kidneys. Some doctors suggest that individuals who have HPRCC, or a family history that suggests HPRCC, should have yearly screening beginning at age 30.

HPRCC is caused by a mutation on the MET gene. The MET gene is a proto-oncogene. Proto-oncogenes make proteins that promote normal cell growth. Mutations in proto-oncogenes result in too much cell growth and can lead to cancer. Genetic testing for mutations in the MET gene is available.

For more information, read the Cancer.Net Guide to Hereditary Papillary Renal Cell Carcinoma.

Birt-Hogg-Dubé syndrome (BHD). BHD is a rare genetic condition associated with multiple benign skin tumors, lung cysts, and an increased risk of both benign kidney tumors and kidney cancer. People with BHD have about a 15% risk of developing kidney cancer. Most of the kidney cancers associated with BHD are classified as the chromophobe type (a rare type of kidney cancer) or oncocytoma (a slow growing type of kidney cancer that rarely spreads), but clear cell and papillary kidney cancers may also occur. Because of the increased risk of kidney cancer, people with BHD should consider yearly screening with ultrasound, MRI, or CT scan beginning at age 25.

BHD is caused by a mutation on the FLCN gene, and genetic testing is available for families who may have BHD.

For more information, read the Cancer.Net Guide to Birt-Hogg-Dubé Syndrome.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC). People with HLRCC develop skin nodules called leiomyomata. The nodules are found mainly on the arms, legs, chest, and back. Women with HLRCC often develop uterine fibroids known as leiomyomas, or, less commonly, leiomyosarcoma. People with HLRCC also have about a 20% risk of developing type 2 papillary renal cell carcinoma.

The most common screening options for people who may have HLRCC are regular skin examinations, abdominal/pelvic CT scans, or MRI every two years. Also, a doctor may recommend that women have regular gynecological examinations and ultrasounds to look for uterine fibroids. HLRCC is caused by the fumarate hydratase (FH) gene, and genetic testing for this gene is available.

For more information, read the Cancer.Net Guide to Hereditary Leiomyomatosis and Renal Cell Carcinoma.

Are there other genetic conditions associated with an increased risk of kidney cancer?

Other genes may be associated with an increased risk of kidney cancer, and finding other genetic causes of kidney cancer is an active area of research. In addition, other genetic conditions may be associated with an increased risk of kidney cancer.

Beckwith-Wiedemann syndrome (BWS). Children with BWS have an increased risk of developing Wilms’ tumor (a type of kidney cancer). BWS is a growth disorder associated with large body size, large tongue, abdominal wall defects, an increased risk of childhood tumors, kidney abnormalities, low blood sugar when a baby is a newborn, and unusual ear creases or pits. Children with BWS may also have body parts that are larger on one side of the body than on the other.

In most people, the genetic changes that cause BWS occur by chance, but others may have inherited changes. Screening for people who may have BWS includes MRI or CT scans of the abdomen, abdominal ultrasound, blood tests, and regular physical examinations.

For more information, read the Cancer.Net Guide to Beckwith-Wiedemann Syndrome.

Li-Fraumeni syndrome (LFS). People with LFS have up to a 50% chance of developing cancer by age 40 and a 90% chance of developing cancer by age 60. Some of the cancers most commonly associated with LFS are osteosarcoma (a type of bone cancer), soft tissue sarcoma, leukemia, breast cancer, brain cancer, and adrenal cortical tumors. An adrenal cortical tumor begins in the adrenal cortex, which is the outer layer of the adrenal glands. The adrenal glands are located on top of each kidney and are a part of the body’s endocrine (hormonal) system. Wilms’ tumor has occasionally been reported in such families, but the risk of developing Wilms’ tumor is not known.

LFS is a rare condition. The gene associated with LFS is called p53. The p53 gene is a tumor suppressor gene. Testing for p53 gene mutations is available for families meeting the diagnostic criteria for LFS. More research is needed to better understand LFS. Another gene, CHEK2, may be responsible for LFS in some families. Testing for mutations in the CHEK2 gene is only available as part of a research study.

For more information, read the Cancer.Net Guide to Li-Fraumeni syndrome.

Tuberous sclerosis complex (TSC). TSC is a genetic condition associated with changes in the skin, brain, kidney, and heart. People with TSC have about a 4% risk of developing kidney cancer. Suggested screening to detect kidney cancer for people who have TSC includes an ultrasound of the kidneys every one to three years, more frequently if necessary, followed by MRI or CT scans of the kidneys if more detail is needed.

TSC is caused by a mutation on either the TSC1 or the TSC2 gene. Although, approximately 60% of people with TSC do not have a family history of the condition.

For more information, read the Cancer.Net Guide to Tuberous Sclerosis Complex.

Cowden syndrome (CS). People with CS have developed kidney cancer. Although, it is not known whether having CS increases a person’s risk of developing kidney cancer. Cowden syndrome is a rare genetic condition caused by a mutation on the PTEN gene. People with CS have a high risk of both benign and cancerous tumors of the breast, thyroid, and endometrium (lining of the uterus). Also, people with CS often have small growths on the face or in the mouth and a larger than average head size.

For more information, read the Cancer.Net Guide to Cowden Syndrome.

What is a person's risk level?

In addition to family history, other environmental and lifestyle factors may increase the risk of kidney cancer. Discussing family history and personal risk factors with a doctor can help someone better understand his or her risk. People with a higher than average risk may benefit from genetic counseling and early detection strategies.

A risk factor is anything that increases a person's risk of developing cancer. Having a particular genetic mutation linked to kidney cancer cannot predict that a person will develop cancer. Research is underway to clarify these risks. Controllable risk factors also play a role. Controllable risk factors include eating a balanced diet, maintaining a healthy weight, exercising, avoiding chemicals and asbestos, limiting alcoholic beverages, and avoiding tobacco products. Some people who develop kidney cancer have few known risk factors. Research to better understand the risk between genetic mutations and kidney cancer is ongoing. Talk with a doctor for more information about risk factors, prevention, and screening for kidney cancer.

More Information

Cancer.Net: Genetics

Cancer.Net Guide to Kidney Cancer

Cancer.Net Guide to Wilms’ Tumor