With therapeutic successes and improved survival after a cancer diagnosis in childhood, increasing numbers of cancer survivors are at risk of subsequent treatment-related morbidities, including cataracts. While it is well known that the lens of the eye is one of the most radiosensitive tissues in the human body, the risks associated with radiation doses less than 2 Gy are less understood, as are the long- and short-term cataract risks from exposure to ionizing radiation at a young age. In this study, we followed 13,902 five-year survivors of childhood cancer in the Childhood Cancer Survivor Study cohort an average of 21.4 years from the date of first cancer diagnosis. For patients receiving radiotherapy, lens dose (mean: 2.2 Gy; range: 0–66 Gy) was estimated based on radiotherapy records. We used unconditional multivariable logistic regression models to evaluate prevalence of self-reported cataract in relationship to cumulative radiation dose both at five years after the initial cancer diagnosis and at the end of follow-up. We modeled the radiation effect in terms of the excess odds ratio (EOR) per Gy. We also analyzed cataract incidence starting from five years after initial cancer diagnosis to the end of follow-up using Cox regression. A total of 483 (3.5%) cataract cases were identified, including 200 (1.4%) diagnosed during the first five years of follow-up. In a multivariable logistic regression model, cataract prevalence at the end of follow-up was positively associated with lens dose in a manner consistent with a linear dose-response relationship (EOR per Gy = 0.92; 95% CI: 0.65–1.20). The odds ratio for doses between 0.5 and 1.5 Gy was elevated significantly relative to doses <0.5 Gy (OR = 2.2; 95% CI: 1.3–3.7). The results from this study indicate a strong association between ocular exposure to ionizing radiation and long-term risk of pre-senile cataract. The risk of cataract increased with increasing exposure, beginning at lens doses as low as 0.5 Gy. Our findings are in agreement with a growing body of evidence of an elevated risk for lens opacities in populations exposed to doses of ionizing radiation below the previously suggested threshold level of 2 Gy.
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