Causes, Risk Factors, and Prevention of Retinoblastoma

Retinoblastoma is a rare cancer of the eye. Most retinoblastoma is diagnosed in young children. Retinoblastoma is a type of eye cancer that usually starts because of a change in a gene called RB1.

What causes retinoblastoma?

Changes in the RB1 genes are responsible for most cases of retinoblastoma. Normally, the RB1 genes help keep cells from growing too fast. Each cell normally has two RB1 genes. As long as a retinal cell has at least one RB1 gene that works as it should, it will not form retinoblastoma. However, when both RB1 genes are damaged, cells can grow out of control, resulting in cancer. However, the cause of damage to this gene is largely unknown.

The RB1 gene is a tumor suppressor gene. In rare cases, changes in the BCOR gene (a tumor suppressor gene) or amplification of MYCN (an oncogene) have been found in retinoblastoma cells. Learn more how these types of genes work on Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes.

Sporadic and heritable changes in RB1

While changes in the RB1 gene account for most cases of retinoblastoma, those gene changes can be sporadic or heritable.

Retinoblastoma due to sporadic RB1 gene changes

Sporadic gene changes are due to chance and start in a single cell. They are present in about 60% of children diagnosed with retinoblastoma. Retinoblastomas caused by a sporadic RB1 gene change:

• Cause tumors that are more likely to occur in only one eye, rather than both
• Are diagnosed in older children than those with heritable RB1 gene changes
• Do not increase the risk of retinoblastoma in an affected child’s future children

Retinoblastoma due to heritable RB1 gene changes

Heritable gene changes affect cells all over the body. They are present in about 40% of children with retinoblastoma. Heritable gene changes can happen early in development, while the child is still in the womb, or children can inherit an RB1 gene change from a parent. Features of retinoblastoma caused by heritable RB1 gene changes include:

• Multifocal (multiple tumors in one eye) or bilateral (affecting both eyes) tumors
• Young age at diagnosis (especially in the first year of life)
• Increased risk of retinoblastoma in an affected child’s future children

Children with heritable RB1 changes have a higher risk of some other types of cancer as they age. For more information, see Hereditary Retinoblastoma.

Risk factors for retinoblastoma

A risk factor is anything that affects the chance of having a disease such as cancer. Different cancers have different risk factors.

Unlike adult cancers, lifestyle-related risk factors such as body weight, physical activity, diet, and the use of tobacco and alcohol do not play a major role in pediatric cancers. In many cases, researchers do not know what causes the gene changes responsible for retinoblastoma. Other potential risk factors for retinoblastoma are still being studied.

Can retinoblastoma be prevented?

In adults, the risk for cancers can be reduced by avoiding certain risk factors, such as smoking or exposure to hazardous chemicals in the workplace. However, there are no known avoidable risk factors for retinoblastoma. If your child has retinoblastoma, it is important to know that you and your child did nothing to cause it.

In some cases, parents who had heritable retinoblastoma can pass on the RB1 gene change that increases cancer risk for their children. People who have had retinoblastoma might want to consider genetic counseling before having children to learn more about the risk of passing on this gene change and perhaps to explore ways to avoid this. For example, an option some people might consider would be to use in vitro fertilization (IVF) and implant only embryos that do not have the gene change.

If a preventive option is not used, children born to a parent with a history of retinoblastoma should be screened carefully starting shortly after birth, because early detection of this cancer greatly improves the chance for successful treatment. For more information on the management and early detection of retinoblastoma in these children, see Hereditary Retinoblastoma.