Virginia Commonwealth University

VCU Massey Cancer Center

Causes and risk factors

It is uncommon for Wilms tumor to run in families. Less than 2 percent of cases will have an affected relative. Most cases of Wilms tumor are considered sporadic (occur by chance) and are the result of genetic mutations that affect cell growth in the kidney. These mutations generally arise after birth, but, in some cases, children are born with a genetic alteration that predisposes them to cancer.

A small percentage of patients with Wilms tumor have one of three genetic syndromes, including the following:

  • WAGR syndrome – the acronym WAGR stands for the four diseases present in WAGR syndrome, including: Wilms tumor, aniridia (absence of the iris, the colored part of the eye), genitourinary malformations and mental retardation. This syndrome is caused by loss or inactivation of a tumor suppressor gene called WT1 on chromosome 11. Tumor suppressor genes usually suppress the growth of tumors and control cell growth. When altered, they no longer control cell growth and tumors may form.
  • Denys-Drash syndrome – characterized by kidney failure, genitourinary malformations and tumors of the gonads (ovaries or testes). This syndrome also is caused by loss or inactivation of a tumor suppressor gene called WT1 on chromosome 11. Tumor suppressor genes usually suppress the growth of tumors and control cell growth. When altered, they no longer control cell growth and tumors may form. 
  • Beckwith-Wiedemann syndrome – characterized by large birthweight and a large liver, spleen and tongue, low blood sugar in neonatal period, malformations around the ear, asymmetric growth of the body, abdominal wall defects near the navel (omphalocele), and tumors of the liver and adrenal glands. This syndrome is thought to be caused by an overactive copy of an oncogene on chromosome 11, called IGF2. Oncogenes control cell growth, but, if mutated, uncontrolled cell growth may result.