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Increased Risk Associated With Radiation Therapy: A Report for the Childhood Cancer Survivor Study

Lillian R. Meacham, MD; Charles A. Sklar, MD; Suwen Li, MS; Qi Liu, MS; Nora Gimpel, MD; Yutaka Yasui, PhD; John A. Whitton, MS; Marilyn Stovall, PhD; Leslie L. Robison, PhD; Kevin C. Oeffinger, MD

Arch Intern Med. 2009;169(15):1381-1388.

Background  Childhood cancer survivors are at increased risk of morbidity and mortality. To further characterize this risk, this study aimed to compare the prevalence of diabetes mellitus (DM) in childhood cancer survivors and their siblings.

Methods  Participants included 8599 survivors in the Childhood Cancer Survivor Study (CCSS), a retrospectively ascertained North American cohort of long-term survivors who were diagnosed between 1970 and 1986 as well as 2936 randomly selected siblings of the survivors. The main outcome was self-reported DM.

Results  The mean ages of the survivors and the siblings were 31.5 years (age range, 17.0-54.1 years) and 33.4 years (age range, 9.6-58.4 years), respectively. Diabetes mellitus was reported in 2.5% of the survivors and 1.7% of the siblings. After adjustment for body mass index, age, sex, race/ethnicity, household income, and insurance, the survivors were 1.8 times more likely than the siblings to report DM (95% confidence interval [CI], 1.3-2.5; P < .001), with survivors who received total body irradiation (odds ratio [OR], 12.6; 95% CI, 6.2-25.3; P < .001), abdominal irradiation (OR, 3.4; 95% CI, 2.3-5.0; P < .001), and cranial irradiation (OR, 1.6; 95% CI 1.0-2.3; P = .03) at increased risk. In adjusted models, an increased risk of DM was associated with total body irradiation (OR, 7.2; 95% CI, 3.4-15.0; P < .001), abdominal irradiation (OR, 2.7; 95% CI, 1.9-3.8; P < .001), use of alkylating agents (OR, 1.7; 95% CI, 1.2-2.3; P < .01), and younger age at diagnosis (0-4 years; OR, 2.4; 95% CI, 1.3-4.6; P < .01).

Conclusion  Childhood cancer survivors treated with total body or abdominal irradiation have an increased risk of diabetes that appears unrelated to body mass index or physical inactivity.

Author Affiliations: Department of Pediatrics, Emory University, and AFLAC Cancer Center and Blood Disorders Service, Atlanta, Georgia (Dr Meacham); Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (Drs Sklar and Oeffinger); Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Canada (Mss Li and Liu and Dr Yasui); Department of Family and Community Medicine, University of Texas Southwestern Medical Center at Dallas (Dr Gimpel); Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington (Mr Whitton); Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston (Dr Stovall); and Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, Tennessee (Dr Robison).

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