Research eyes risk of second cancers occurring in retinoblastoma patients

Chance of getting, dying from non-ocular malignancies differs between men, women

The 10-year survival rate for patients with hereditary retinoblastoma is excellent, but these individuals are at increased risk for developing secondary cancers and have elevated mortality compared to age-matched individuals in the general population.

According to analyses of data for retinoblastoma patients in the United States, there are gender-related differences in both the incidence of the different types of second non-ocular malignancies and cause-specific mortality, said Ruth Kleinerman, PhD.

Related: Retinoblastoma screening rules set foundation for care 

“Based on this information, evidence-based guidelines for longterm surveillance and follow-up of retinoblastoma survivors should take gender into account,” said Dr. Kleinerman, deputy branch chief, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD. “International pooling of second cancer data for retinoblastoma survivors will increase the number of cases of second cancers and provide statistical power to further investigate gender disparity in risk with greater precision.”

Information on the incidence of second cancers in retinoblastoma survivors and rates of mortality related to the subsequent cancers is available from the National Cancer Institute Long-term Follow-up Study of Retinoblastoma Survivors.

It includes data on 1,129 patients with hereditary retinoblastoma diagnosed between 1914 through 2006, of whom approximately 50% were still alive in 2016.

Dr. Kleinerman said that the most common second cancers in the hereditary retinoblastoma survivors are bone cancer, soft tissue sarcoma, and melanoma. Analyses of cause-specific mortality compare the rates of death among retinoblastoma survivors with those reported for the U.S. population.

The data show that female retinoblastoma survivors have a higher risk of dying of bone cancer, melanoma, and brain tumors and a slightly higher risk of dying of nasal cavity cancers compared with females in the general population.

Rates of death due to lung, bladder, and colon cancer among female retinoblastoma survivors also appear to be higher than females in the general population. Male retinoblastoma survivors are at higher risk of dying of pancreatic cancer than males in the general population.

Related: Retinoblastoma survival rates high; secondary cancer a riskWhy the increased risk?
Genetic susceptibility, treatment, and other factors might contribute to the increased risk of second cancers in patients with hereditary retinoblastoma.

Hereditary retinoblastoma is caused by germline mutations in RB1, and the location of the mutation or the type of the mutation may be involved in the risk of some secondary cancers, including lung, bladder, and brain tumors. In addition, the patients may be carrying mutations in other related pathways.

The RB1 gene is the spark for the creation of a protein called pRB, which acts as a tumor suppressor, meaning that it regulats cell growth and keeps cells from dividing to fast or in an uncontrolled way. The RB1 gene provides instructions for making a protein called pRB.

This protein acts as a tumor suppressor, which means that it regulates cell growth and keeps cells from dividing too fast or in an uncontrolled way.

“For example, RB1 is in the same cell cycle control pathway as CDKN2A, which is a susceptibility gene for familial melanoma and pancreatic cancer,” Dr. Kleinerman said. Host characteristics, such as age and sex, as well as lifestyle and environmental factors, such as smoking history and sun exposure, may also play a role.

Host characteristics, such as age and sex, as well as lifestyle and environmental factors, such as smoking history and sun exposure, may also play a role.

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Ruth Kleinerman, PhD

E: kleinerr@exchange.nih.gov

This article is based on a presentation given by Dr. Kleinerman at the Ocular Oncology/Pathology Subspecialty Day meeting. The mortality data were subsequently published in the Journal of the National Cancer Institute (Kleinerman RA, et al. Patterns of causespecifi c mortality among 2053 survivors of retinoblastoma, 1914-2016.

J Natl Cancer Ins

t. 2019 Jan 30. Doi: 10.1093/jnci/djy227 [Epub ahead of print]).

Dr. Kleinerman has no relevant financial interests to disclose.