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.

Expert review and references

  • American Cancer Society. Causes, Risk Factors and Prevention. 2015.
  • American Society of Clinical Oncology. Retinoblastoma - Childhood. 2017: http://www.cancer.net/cancer-types/retinoblastoma-childhood/view-all.
  • Azary S, Ganguly A, Bunin GR, Lombardi C et al . Sporadic retinoblastoma and parental smoking and alcohol consumption before and after conception: a report from the Children's Oncology Group. PLoS One. 2016.
  • Bradbury BD & Jick H . In vitro fertilization and childhood retinoblastoma. British Journal of Clinical Pharmacology. Wiley Online; 2004.
  • Bunin GR, Felice MA, Davidson W, et al . Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation. International Journal of Cancer. Hoboken, NJ: Wiley-Liss, Inc; 2011.
  • Bunin GR, Meadows AT, Emanuel BS, et al . Pre- and postconception factors associated with sporadic heritable and nonheritable retinoblastoma. Cancer Research. American Association for Cancer Research; 1989.
  • Bunin GR, Petrakova A, Meadows AT, et al . Occupations of parents of children with retinoblastoma: a report from the Children's Cancer Study Group. Cancer Research. American Association for Cancer Research; 1990.
  • Cancer Research UK. Eye cancer (retinoblastoma). Cancer Research UK; 2015.
  • Children's Hospital Boston. Retinoblastoma. Boston, MA: Children's Hospital Boston; 2017.
  • DerKinderen DJ, Koten JW, Tan KE, et al . Parental age in sporadic hereditary retinoblastoma. American Journal of Ophthalmology. Elsevier; 1990.
  • Dockerty JD, Draper G, Vincent T, et al . Case-control study of parental age, parity and socioeconomic level in relation to childhood cancers. International Journal of Epidemiology. Oxford, UK: Oxford Journals Oxford University Press; 2001.
  • Heck JE, Contreras ZA, Park AS, Davidson TB, Cockburn M, Ritz B . Smoking in pregnancy and risk of cancer among young children: a population-based study. International Journal of Cancer. 2016.
  • Hurwitz RL, Shields CL, Shields JA et al . Retinoblastoma. Pizzo PA & Poplack DG (eds.). Principles and Practice of Pediatric Oncology. 7th ed. Philadelphia: Wolters Kluwer; 2016: 27: 700-725.
  • Retinoblastoma. Janes-Hodder, H. & Keene, N. Childhood Cancer - A Parent's Guide to Solid Tumor Cancers. 2nd ed. O'Reilly; 2002: 13: pp.193-205.
  • MacCarthy A, Bunch KJ, Fear NT, et al . Paternal occupation and retinoblastoma: a case-control study based on data for Great Britain 1962-1999. Occupational and Environmental Medicine. BMJ Publishing Group; 2009.
  • Macmillan Cancer Support . Retinoblastoma in children. Macmillan Cancer Support. London, UK: Macmillan Cancer Support; 2011.
  • Macmillan Cancer Support. Retinoblastoma in children. 2016.
  • Marees T, Dommering CJ, Imhof SM, et al . Incidence of retinoblastoma in Dutch children conceived by IVF: an expanded study. Human Reproduction. Oxford University Press; 2009.
  • Martini FH, Timmons MJ, Tallitsch RB. Human Anatomy. 7th ed. San Francisco: Pearson Benjamin Cummings; 2012.
  • Moll AC, Imhof SM, Cruysberg JR, et al . Incidence of retinoblastoma in children born after in-vitro fertilisation. Lancet. New York, NY: Elsevier, Inc; 2003.
  • Moll AC, Imhof SM, Kuik DJ, et al . High parental age is associated with sporadic hereditary retinoblastoma: the Dutch retinoblastoma register 1862-1994. Human Genetics. Springer; 1996.
  • National Cancer Institute. Retinoblastoma Treatment (PDQ®) Health Professional Version. 2016.
  • Retinoblastoma. National Institutes of Health. Genetics Home Reference. Bethesda, MD: U.S. National Library of Medicine; 2009.
  • Ross, J.A. & Spector, L.G . Cancers in children. Schottenfeld, D. & Fraumeni, J. F. Jr. (Eds.). Cancer Epidemiology and Prevention. 3rd ed. New York: Oxford University Press; 2006: 65: 1252-1268.
  • Robert C, Karaszewska B, Schachter J, et al . Improved overall survival in melanoma with combined dabrafenib and trametinib . Lancet Oncology . 372(1):30-39 .
  • St. Jude Children's Research Hospital. Retinoblastoma. Memphis, TN: St. Jude Children's Research Hospital; 2017.
  • Stavrou EP, Baker DF, Bishop JF . Maternal smoking during pregnancy and childhood cancer in New South Wales: a record linkage investigation. Cancer Causes & Control. Springer; 2009.
  • Theriault BL, Dimaras H, Gallie BL, Corson TW . The genomic landscape of retinoblastoma: a review. Clinical and Experimental Ophthalmology. 2014.

Medical disclaimer

The information that the Canadian Cancer Society provides does not replace your relationship with your doctor. The information is for your general use, so be sure to talk to a qualified healthcare professional before making medical decisions or if you have questions about your health.

We do our best to make sure that the information we provide is accurate and reliable but cannot guarantee that it is error-free or complete.

The Canadian Cancer Society is not responsible for the quality of the information or services provided by other organizations and mentioned on cancer.ca, nor do we endorse any service, product, treatment or therapy.

1-888-939-3333 | cancer.ca | © 2024 Canadian Cancer Society