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.