Every year, about 62,000 people in the United States are diagnosed with kidney cancer. If you or a loved one is among them, you may be wondering why this type of cancer developed. As with most cancers, there are many risk factors that can increase the chances of developing kidney cancer. Some of these are inherited — meaning they’re passed down from biological parents — and can increase a person’s risk.

In this article, we’ll explore how kidney cancer can sometimes run in families. We’ll look at the main genetic syndromes linked to kidney cancer, how common they are, and how to find out whether genetic screening might be right for you.

What Is Hereditary Kidney Cancer?

A hereditary cancer syndrome is a condition in which mutations (changes) in certain genes increase a person’s risk of developing cancer. These mutations are passed down through families, from parent to child. Depending on the gene involved, a person with a hereditary cancer condition may be at risk for one specific type of cancer, such as kidney cancer, or several different types.

Hereditary kidney cancer makes up about 5 percent to 8 percent of all kidney cancer diagnoses. The inherited syndromes we’ll discuss in this article are mostly associated with a type of kidney cancer called renal cell carcinoma (RCC), the most common form of kidney cancer.

RCC makes up 85 percent of all kidney cancer cases. In RCC, tumors start in the kidney tubules. These tiny tubes inside your kidneys filter and clean your blood, making urine.

In most people, kidney cancer isn’t related to a specific inherited syndrome. Many environmental and lifestyle factors have been linked to an increased risk of developing kidney cancer. These include:

• Smoking
• Obesity — A medical condition in which a person’s body mass index (BMI), a measure of weight relative to height, is 30 or higher
• Hypertension (high blood pressure)
• Exposure to certain workplace chemicals — Includes trichloroethylene (a metal-cleaning solvent) and cadmium (a toxic metal found in batteries)

What Hereditary Syndromes Can Cause Kidney Cancer?

In addition to environmental and lifestyle factors, certain inherited syndromes can significantly increase the risk of kidney cancer. Here are four major hereditary conditions linked to a higher likelihood of developing kidney cancer.

Von Hippel-Lindau Disease

Von Hippel-Lindau (VHL) disease is an inherited condition that increases a person’s risk for developing several types of tumors, both cancerous and benign (noncancerous). People with this condition inherit a pathogenic (harmful) variant in the VHL gene. Normally, the VHL gene helps to suppress the formation of tumors. When this gene doesn’t function properly, tumors are more likely to form.

If you are the child of a person with VHL, you have a 50 percent chance of inheriting the condition from your parents.

VHL is the most common inherited form of kidney cancer, though it’s still rare — affecting about 1 in 31,000 to 1 in 91,000 people worldwide. Most people with a confirmed VHL diagnosis develop one or more tumors by the age of 65.

People with VHL have an estimated 25 percent to 45 percent lifetime risk of developing renal cell carcinoma over their lifetime, and the average age of diagnosis is around 37. They may also be at increased risk for other types of tumors, including those in the brain, spine, eyes, pancreas, and adrenal glands.

If you or someone in your family has VHL, or you suspect you may be at risk, talk to your doctor about genetic testing and early screening. Regular monitoring can help detect tumors early, when they’re easier to treat.

Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé (BHD) syndrome is an inherited condition caused by mutations in a gene called FLCN, which provides instructions for making a protein called folliculin. This protein plays a role in how cells grow, survive, and divide.

BHD syndrome is very rare — studies have estimated that only 1 in 200,000 to 1 in 500,000 people have this syndrome.

Like in VHL disease, people with BHD syndrome are at increased risk of developing different types of tumors, including kidney cancer. About 15 percent to 30 percent of people with BHD syndrome can develop kidney cancer. These cancers are usually slow-growing. The average age of diagnosis for kidney tumors is 46 to 50 years.

A distinctive feature of BHD syndrome is the appearance of multiple small, benign papules (skin growths) on the face, neck, and upper chest. These growths occur in about 73 percent to 84 percent of people with BHD.

BHD is inherited in an autosomal dominant pattern, meaning each child of a parent with the syndrome has a 50 percent chance of inheriting the condition.

Hereditary Leiomyomatosis and Renal Cell Cancer

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited condition that can lead to the development of three types of tumors:

• Cutaneous leiomyomas — Small, raised skin tumors
• Uterine fibroids — Noncancerous growths in the uterus that can cause heavy periods, pain, or pressure
• Renal cell carcinoma

HLRCC is caused by mutations in the fumarate hydrase (FH) gene, which are passed down from parent to child. Recent studies are showing that HLRCC is more common than previously thought. It may affect as many as 1 in 2,700 people who carry the FH gene mutation, which means they have the condition even if they don’t yet show symptoms.

Most people with HLRCC develop at least one of these three tumor types at some point during their lives. Earlier studies estimated that 15 percent to 30 percent of people with HLRCC develop renal cell cancer. However, more recent data suggest this number may be lower, since many people with HLRCC may go undiagnosed.

As with other hereditary kidney cancer syndromes, frequent lifelong screening is necessary for people with HLRCC. The renal cell carcinoma that people with this condition develop tends to be aggressive. This means that early detection and treatment are important for the best outcomes.

Hereditary Papillary Renal Carcinoma

Hereditary papillary renal carcinoma (HPRC) is a rare inherited condition caused by mutations in the MET gene, which are passed from parent to child. HPRC is estimated to affect about 1 in 500,000 people.

Everyone with this condition is expected to develop a type of kidney cancer called papillary renal cell carcinoma, a subtype of renal cell carcinoma. Unlike other hereditary kidney cancer syndromes, HPRC is only known to cause kidney cancer — no other tumor types have been linked to it.

The average age of diagnosis is around 42 years, and people with HPRC should undergo regular screening throughout their lives to detect tumors early, when they’re more treatable.

Other Hereditary Kidney Cancer-Associated Conditions

In addition to the syndromes already discussed, several other inherited conditions can increase a person’s risk of developing kidney cancer. These include:

• Hereditary paraganglioma-pheochromocytoma syndromes
• Cowden syndrome
• Tuberous sclerosis
• BAP1 tumor predisposition syndrome
• Sickle cell disease

These conditions vary in how strongly they are linked to kidney cancer and in the types of tumors they may cause.

Who Should Be Screened for Inherited Kidney Cancer Syndromes?

If you or a close relative has had kidney cancer — especially at a young age — it’s important to talk to your healthcare provider about your family history.

Genetic screening may be recommended if you have:

• A relative with a confirmed diagnosis of one of the inherited conditions listed in this article
• A personal or family history of multiple tumors linked to these syndromes
• A known mutation in a gene associated with hereditary kidney cancer

Screening can help identify people at risk before symptoms appear, allowing for early monitoring and treatment when needed.

Talk With Others Who Understand

MyKidneyCancerTeam is the social network for people with kidney cancer and their loved ones. On MyKidneyCancerTeam, members come together to ask questions, give advice, and share their stories with others who understand life with kidney cancer.

Have you or a loved one been diagnosed with kidney cancer? Are you wondering about your risk for inherited kidney cancer? Share your experiences in the comments below, or start a conversation by posting to your Activities feed.