Medical radiation exposure and risk of retinoblastoma: A report from the Children’s Oncology Group

Authors: Shakeel O, Pace N, Scheurer ME, Lupo PJ, Ganguly A, Bunin GR

Category: Molecular Epidemiology & Environment
Conference Year: 2019

Abstract Body:
Purpose: To evaluate the role of paternal medical radiation exposure on sporadic bilateral and unilateral retinoblastoma in offspring.Methods: Eligible patients were diagnosed with sporadic bilateral or unilateral retinoblastoma from 1998 to 2011 and treated at one of nine participating institutions. Controls were recruited from the friends and relatives of cases. Telephone interviews were conducted with parents to obtain information on demographic factors and exposures, including medical procedures prior to conception of the index child. Gonadal radiation doses were estimated utilizing PCXMC and ImPACT software. Logistic regression models were used to evaluate the associations between parental medical radiation exposure and retinoblastoma.Results: In maternal analyses, there were 298 bilateral cases, 184 unilateral cases, and 404 controls. In paternal analyses, there were 268 bilateral cases, 155 unilateral cases, and 358 controls. We found that compared to mothers without medical radiation exposure, mothers who reported a lower gastrointestinal (GI) series were more likely to have a child who developed bilateral retinoblastoma (odds ratio [OR]=6.9, 95% confidence interval [CI]: 2.9-16.4). A similar association was observed for unilateral retinoblastoma though the confidence interval included the null (OR=2.8, 95% CI: 0.8-9.7). When evaluating gonadal dose, increasing maternal exposure was associated with bilateral retinoblastoma (P for trend=0.03). Further, compared to unexposed mothers, mothers in the highest dose category were more likely to have a child who developed sporadic bilateral retinoblastoma (OR=2.3, 95% CI: 1.4-4.1). Notably, the same trend was not observed for unilateral retinoblastoma. Transversely, increasing paternal gonadal dose was associated with unilateral retinoblastoma (P for trend=0.03) but not bilateral retinoblastoma.Conclusions: These results are in contrast to previously hypothesized patterns (i.e., that maternal exposure would be associated with unilateral retinoblastoma, whereas paternal exposure would be associated with bilateral retinoblastoma due to a de novo mutation in RB1 of paternal origin). Our findings could point to a more complex etiologic framework for this important pediatric malignancy.

Keywords: Retinoblastoma, Medical Radiation