Personal history of diabetes, genetic susceptibility to diabetes, and risk of brain glioma: a pooled analysis of observational studies.
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
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.
Cari M
CM
Kitahara
Martha S
MS
Linet
Alina V
AV
Brenner
Sophia S
SS
Wang
Beatrice S
BS
Melin
Zhaoming
Z
Wang
Peter D
PD
Inskip
Laura E Beane
LE
Freeman
Melissa Z
MZ
Braganza
Tania
T
Carreón
Maria
M
Feychting
J Michael
JM
Gaziano
Ulrike
U
Peters
Mark P
MP
Purdue
Avima M
AM
Ruder
Howard D
HD
Sesso
Xiao-Ou
XO
Shu
Martha A
MA
Waters
Emily
E
White
Wei
W
Zheng
Robert N
RN
Hoover
Joseph F
JF
Fraumeni
Nilanjan
N
Chatterjee
Meredith
M
Yeager
Stephen J
SJ
Chanock
Patricia
P
Hartge
Preetha
P
Rajaraman
D000368:Aged; D001932:Brain Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005910:Glioma / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology