Background: Brain glioma is a relatively rare and fatal malignancy in adulthood with fewknown risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear. Methods: Weconducted a pooled analysis of original data fromfive nested case-control studies and two case- control studies fromtheUnited States and China that included 962 glioma cases and 2,195 controls. Weexamined self-reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma riskassociated single-nucleotide polymorphisms(SNP). We also examined the associations between 13 diabetes riskassociated 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 diabetesrelated 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. Cancer Epidemiol Biomarkers Prev; 23(1); 47-54.
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