Retinoblastoma

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Causes, Risk Factors, and Prevention TOPICS

Do we know what causes retinoblastoma?

Retinoblastoma is caused by mutations (changes) in certain genes. Over the past few decades, scientists have made great progress in learning how certain changes in a person’s DNA can cause cells of the retina to become cancerous. DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects much more than just the way we look.

Some genes have instructions that control when our cells grow, divide into new cells, and die. Certain genes that help cells grow, divide, or stay alive are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

The most important gene in retinoblastoma is the RB1 tumor suppressor gene. This gene makes a protein (pRb) that helps stop cells from growing too quickly. Each cell normally has 2 RB1 genes. As long as a retinal cell has at least one RB1 gene that works as it should, it will not form a retinoblastoma. But when both of the RB1 genes are mutated or missing, a cell can grow unchecked. This can lead to further gene changes, which in turn may cause cells to become cancerous.

Hereditary or bilateral retinoblastoma

About 1 out of 3 children with retinoblastoma have a germline mutation in one RB1 gene; that is, all the cells in the body have a defective RB1 gene. In most of these children (75%), this mutation developed after conception while in the womb. The other 25% of children have inherited it from one of their parents.

About 9 of 10 children who are born with this germline mutation of the RB1 gene develop retinoblastoma. This happens when the second RB1 gene is lost or mutated. Most often the retinoblastoma is bilateral (in both eyes), but sometimes it is found early enough that it is still only in one eye.

These children have hereditary retinoblastoma. All bilateral retinoblastomas are considered hereditary, although not all hereditary retinoblastomas are bilateral (in both eyes) when they are found.

Every person has 2 RB1 genes but passes only 1 on to each of their children (the child gets the other RB1 gene from the other parent). Therefore there is a 1 in 2 chance that a parent who had hereditary retinoblastoma will pass the mutated gene on to his or her child.

Most children with hereditary retinoblastoma don’t have an affected parent (the RB1 gene mutates in the womb). But these children will eventually be at risk of passing the disease on to their children. This is why we call this form of retinoblastoma “hereditary” (even though neither of the child’s parents may have been affected).

Non-hereditary (sporadic) retinoblastoma

Most of the remaining 2 out of 3 children with retinoblastoma do not have the RB1 gene mutation in all the cells of the body. Instead, the RB1 mutation happens early in life and first occurs only in one cell in one eye.

Whether the changes in the RB1 gene are hereditary or sporadic, it is not known what causes these changes. They may result from random gene errors that sometime occur when cells divide to make new cells. There are no known lifestyle-related or environmental causes of retinoblastomas, so it is important to remember that there is nothing these children or their parents could have done to prevent these cancers.


Last Medical Review: 12/05/2013
Last Revised: 12/05/2013