• Authors' Affiliations: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda; Core Genotyping Facility, National Cancer Institute, SAIC-Frederick, Inc., Gaithersburg, Maryland; Division of Cancer Etiology, Department of Population Sciences, City of Hope and the Beckman Research Institute, Duarte, California; Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, Ohio; Division of Preventive Medicine; Division of Aging, Brigham and Women's Hospital, Harvard Medical School; Massachusetts Veterans Epidemiology, Research and Information Center, Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts; Fred Hutchinson Cancer Research Center; Department of Epidemiology, University of Washington, Seattle, Washington; Vanderbilt University Medical Center, Nashville, Tennessee; Department of Radiation Sciences, Oncology, Umeå University, Umeå; and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

BACKGROUND: Brain glioma is a relatively rare and fatal malignancy in adulthood with few known risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear.

METHODS: We conducted a pooled analysis of original data from five nested case-control studies and two case-control studies from the United States and China that included 962 glioma cases and 2,195 controls. We examined self-reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma risk-associated single-nucleotide polymorphisms (SNP). We also examined the associations between 13 diabetes risk-associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted logistic regression models.

RESULTS: We observed a 42% reduced risk of glioma for individuals with a history of diabetes (OR = 0.58; 95% CI, 0.40-0.84). The association did not differ by sex, study design, or after restricting to glioblastoma, the most common histological subtype. We did not observe any significant per-allele trends among the 13 diabetes-related SNPs examined in relation to glioma risk.

CONCLUSION: These results support an inverse association between diabetes history and glioma risk. The role of genetic susceptibility to diabetes cannot be excluded, and should be pursued in future studies together with other factors that might be responsible for the diabetes-glioma association.

IMPACT: These data suggest the need for studies that can evaluate, separately, the association between type 1 and type 2 diabetes and subsequent risk of adult glioma.