Personal history of diabetes, genetic susceptibility to diabetes, and risk of brain glioma: a pooled analysis of observational studies.
Kitahara-CM; Linet-M; Brenner-AV; Wang-SS; Melin-B; Wang-Z; Inskip-PD; Beane Freeman-L; Braganza-MZ; Carreon-T; Feychting-M; Gaziano-JM; Peters-U; Purdue-MP; Ruder-A; Sesso-HD; Shu-XO; Waters-M; White-E; Zheng-W; Hoover-RN; Fraumeni-JF Jr.; Chatterjee-N; Yeager-M; Chanock-SJ; Hartge-P; Rajaraman-P
Cancer Epidemiol Biomark Prev 2014 Jan; 23(1):47-54
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 U.S. 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 (SNPs). We also examined the associations between 13 diabetes risk-associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (ORs) and 95% confidence intervals (CIs) 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 sub-type. 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.
Endocrine-function; Endocrine-system-disorders; Cancer; Brain-disorders; Central-nervous-system-disorders; Epidemiology; Statistical-analysis; Case-studies; Genetics; Genetic-factors;
Author Keywords: diabetes mellitus; brain cancer; glioma; cancer; epidemiology
Cari M. Kitahara, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, MD, 20892, United States
Cancer Epidemiology, Biomarkers & Prevention
MD; CA; OH; MA; WA; TN