Abstract
BACKGROUND: Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are common early-onset malignancies. Their causes are largely unknown but infectious etiology has been implicated. Type 1 diabetes (T1D) is an autoimmune disease for which infectious triggers of disease onset have been sought and increasing pointing to enteroviruses. Based on our previous results on co-morbidity between leukemia and T1D, we updated the Swedish dataset and focused on early onset leukemias in patients who had been hospitalized for T1D, comparing to those not hospitalized for T1D. METHODS AND FINDINGS: Standardized incidence ratios (SIRs) were calculated for leukemia in 24,052 patients hospitalized for T1D covering years 1964 through 2008. T1D patients were included if hospitalized before age 21 years. Practically all Swedish children and adolescents with T1D are hospitalized at the start of insulin treatment. SIR for ALL was 8.30 (N = 18, 95% confidence interval 4.91-13.14) when diagnosed at age 10 to 20 years after hospitalization for T1D and it was 3.51 (13, 1.86-6.02) before hospitalization for T1D. The SIR for ALL was 19.85 (N = 33, 13.74-27.76) and that for AML was 25.28 (8, 10.80-50.06) when the leukemias were diagnosed within the year of T1D hospitalization. The SIRs increased to 38.97 (26, 25.43-57.18) and 40.11 (8, 17.13-79.42) when T1D was diagnosed between ages 10 to 20 years. No consistent time-dependent changes were found in leukemia risk. CONCLUSION: A shared infectious etiology could be a plausible explanation to the observed co-morbidity. Other possible contributing factors could be insulin therapy or T1D related metabolic disturbances.