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Risk factors for retinoblastoma

A risk factor is something that increases the risk of developing cancer. It could be a behaviour, substance or condition. Most cancers are the result of many risk factors. Mutations or changes in the retinoblastoma 1 (RB1) gene is the most important risk factor for retinoblastoma.

Retinoblastoma accounts for about 2% of all cancers that occur in children 0 to 14 years of age. It most often affects children younger than 5. Most cases of retinoblastoma are diagnosed in children younger than 2.

The following are risk factors for retinoblastoma. All of the risk factors are not modifiable. This means that you can’t change them. Until we learn more about these risk factors, there are no specific ways you can reduce your risk.

Risk factors are generally listed in order from most to least important. But in most cases, it is impossible to rank them with absolute certainty.

Risk factors

RB1 gene mutation

Amplification of the MYCN gene

There is convincing evidence that the following factors increase your risk for retinoblastoma.

RB1 gene mutation

Gene mutations are changes to a gene, which can increase the risk of developing cancer. Retinoblastoma is caused by mutations to the RB1 gene in the retinoblasts, which causes them to grow out of control. There are 2 copies of the RB1 gene in every cell – one from the mother and one from the father. There must be a change in both copies of the RB1 gene for a retinoblastoma tumour to develop.

Non-hereditary retinoblastoma (also called sporadic retinoblastoma) happens by chance. Children are born with 2 normal copies of the RB1 gene. A mutation of both copies of the RB1 gene occurs in a retinoblast causing retinoblastoma to form. Children with non-hereditary retinoblastoma only develop a tumour in one eye. They will not pass the RB1 mutation on to their children. About 60% of retinoblastomas are non-hereditary.

Hereditary retinoblastoma is passed on from a parent to a child. With hereditary retinoblastoma, a child is born with one copy of the RB1 mutation in all cells of the body. A mutation of the second copy of the RB1 gene occurs in retinoblasts causing retinoblastoma to form. Children with hereditary retinoblastoma can have more than one tumour and tumours can occur in one eye (called unilateral retinoblastoma) or both eyes (called bilateral retinoblastoma). They can pass the RB1 mutation on to their children. About 40% of retinoblastomas are hereditary.

Children with hereditary retinoblastoma have a higher risk of developing tumours in the pineal gland (called trilateral retinoblastoma). The pineal gland is a gland in the brain that controls the sleep cycle and plays a role in sexual maturation. Trilateral retinoblastoma usually occurs 20 months or more after retinoblastoma is diagnosed.

Children with hereditary retinoblastoma also have a higher risk of developing these other types of cancer later in life:

  • bone cancer
  • soft tissue sarcoma
  • melanoma skin cancer

Amplification of the MYCN gene

A small number of children with retinoblastoma do not have an RB1 mutation. Instead, retinoblastoma is caused by an increased number of copies (called amplification) of the MYCN gene. Retinoblastoma related to MYCN causes large tumours in one eye and occurs in children younger than 6 months old. It cannot be passed on to children and does not increase the risk of developing other cancers.

Possible risk factors

The following factors have been linked with retinoblastoma, but there is not enough evidence to show for sure that they are risk factors. More research is needed to clarify the role of these factors for retinoblastoma.

  • being born to older parents
  • being born to a mother who smoked during pregnancy

Questions to ask your healthcare team

Ask your child’s healthcare team questions about risks.