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Objective Ionizing radiation is a human carcinogen, but there are uncertainties about cancer risks from long-term exposure at low-doses. Large-scale occupational studies provide opportunities to estimate these risks, yet to date, most have relied on mortality outcomes to do so. This study sought to characterize the risk of incident cancers in relation to cumulative occupational exposure to radiation among nuclear power plant workers in the recently extended follow-up of the Canadian National Dose Registry.Methods This retrospective cohort study comprised 75,350 Canadians employed between 1945 and 2010. Record linkage to national cancer incidence and mortality registries was performed to identify incident cancers between 1969 and 2010. Annual whole-body doses to internal and external ionizing radiation, expressed as effective doses, were determined from personal dosimetry records. Standardized incidence ratios (SIRs) were calculated to compare site-specific cancer rates with the Canadian general population, while Poisson regression models estimated linear excess relative risks (ERR) per 100 millisieverts (mSv) of cumulative exposure.Results A total of 4,370 first primary cancers were identified during the follow-up. The mean cumulative effective dose was 12.0 mSv (SD = 30.42 mSv) at the end of follow-up. Elevated SIRs were observed for malignant melanoma, prostate, and colon cancer, while that for lung cancer incidence was less than one. The ERR estimates were positive, though not statistically significant, for prostate cancer (ERR/100mSv = 0.12; 95% CI: -0.05, 0.29) and melanoma (ERR/100mSv = 0.32; 95% CI: -0.23, 0.87), whereas an inverse association was exhibited for lung cancer. For prostate cancer, age at first exposure was found to modify the risk, with those first exposed from 55 years of age onwards most vulnerable.Conclusion Our findings provide some evidence that low-dose protracted ionizing radiation exposure increases the risk of prostate cancer and malignant melanoma.Funding This project was funded by the Canadian Institutes of Health Research (Funding Application #: 487910).