A renal/urinary tract cancer occurs when cells in the kidney, bladder, or other part of the urinary tract grow abnormally, interfering with normal function. While most are not, approximately 5-8% of renal (kidney) tumors are inherited and hereditary renal/urinary tract cancers (HRUC) occur when a person has a genetic change (mutation) that causes their cells to be more likely to become cancerous. The mutation can be passed through generations in a family. People with HRUC have a higher risk to develop cancer along their urinary tract, and sometimes other cancers or health problems, as well. HRUC can present in early childhood or adulthood.

Hereditary Breast and Ovarian Cancer (HBOC) Our genes, or DNA, tell the cells in our body how to work correctly. Cancer-risk genes are genes with roles that can impact whether a cell will begin to grow uncontrollably into cancer. We have two copies of every gene, one from our mother and the other from our father. HRUC is most commonly inherited in an autosomal dominant way. For dominant conditions, having only one copy of a gene mutation is enough to cause symptoms. In the case of HRUC, having one mutation leads to an increased risk for cancer. If a person has a mutation in one gene for HRUC, there is a 50% risk that each of their children will inherit this mutation. Siblings, parents, and potentially other relatives could also have the mutation. Importantly, not everyone who has a mutation in a cancer-risk gene will develop cancer, but their chances are higher. While rare, it is possible for a person to have a mutation for a dominant condition that is absent from both of their parents. In this situation, the mutation arose early before they were conceived or born. This is called de novo inheritance. Even after de novo inheritance, if a person has a mutation in one gene for hereditary renal or urinary tract cancer, each of their children will have a 50% risk to inherit the mutation.

Autosomal recessive (AR)

Less commonly, HRUC can also be inherited in an autosomal recessive way. For AR conditions, both copies of a person’s gene must have a mutation before they will have the condition. Autosomal conditions occur regardless of whether a person is male or female. Typically, an individual with an AR condition will have inherited one mutation from their mom and one from their dad. Because the mom and dad have another copy of the gene without the mutation, they will usually not show symptoms. For these parents, there is a 25% chance with each pregnancy that the child will inherit both the mom’s and the dad’s mutations, and therefore, will have the recessive condition. Similarly, for a person with autosomal recessive HRUC to have an affected child, their partner would also need to have a mutation in the same gene that causes their HRUC. While the risk is low, partner testing is available.

X-linked recessive (XLR)

In rare cases, HRUC can be caused by a gene mutation located on the X chromosome. A chromosome is the physical structure that carries our genes. Females have two X chromosomes while males only have one. Therefore, for every gene that is located on the X chromosome, males have one copy, while females have two. Because males only have one copy, if a HRUC cancer-risk gene on the X chromosome has a mutation, males do not have a second copy to compensate. Therefore, they will have the condition. Because females have two copies, females with only one mutation for XLR HRUC will usually not show symptoms. These women are called “carriers.” When a carrier female has children, there is a 50% chance that each son will have HRUC, and a 50% chance that each daughter will also be a carrier like her mother.

Von Hippel Lindau (VHL)

People with VHL are at an increased risk for many different types of cancer, including pheochromocytoma, hemangioblasoma, renal cell carcinoma and other neuroendocrine tumors. Von Hippel Lindau is caused by a mutation in the VHL gene. Almost everyone who has a mutation will eventually develop symptoms by age 65 years. Approximately 70% of people with VHL will develop renal cell carcinoma.

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)

Dominant mutations in the FH gene cause HLRCC. The majority of people with this condition develop one or more growths or nodules (cutaneous leiomyomata) on the trunk, arms or legs, usually in their mid-20’s. Women with HLRCC tend to develop numerous, large uterine fibroids. Up to 16% of people with HLRCC will develop renal cancer.

Lynch syndrome

Lynch syndrome, also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is caused by a mutation in a gene whose job is to repair the DNA damage that normally occurs as cells grow and divide. People with Lynch syndrome are at an increased risk for different types of cancers, such as ovarian, gastric, prostate and brain. This is especially true for colon and endometrial cancer. Both men and women with this syndrome have up to an 80% risk to develop colon cancer by age 70 years. Women with Lynch syndrome have up to a 60% chance to develop endometrial cancer. In Lynch syndrome, the chance to develop urinary tract cancer (1-3%) is comparatively small, but is still significantly higher than the general population. Because of the high risk for cancer, people with Lynch syndrome require increased screening earlier than those without the condition.


 A positive result means that one or more genetic mutations for HRUC were identified, confirming a diagnosis. Knowing the specific gene involved tells you how the increased risk for renal/urinary tract cancer in your family was inherited, and can give a doctor insight into the patient’s risk for cancer and other health conditions.


 A negative result indicates that a genetic mutation was not identified. A negative result may indicate that hereditary renal/ urinary tract cancer is not the correct diagnosis. However, it can also mean that the correct gene for HRUC in your family was not included on the ordered test, or even that it is not currently known.


The third possible test result is called a Variant of Uncertain Clinical Significance. A gene variant is a genetic difference that could be disease-causing (mutation) or could be a normal finding (benign). More research is needed to determine whether the variant is important or not, and it should usually be treated as a negative result until more information is available.