Common variation in genes related to innate immunity and risk of adult glioma.
Current evidence suggests that immune system alterations contribute to the etiology of adult glioma, the most common adult brain tumor. Although previous studies have focused on variation in candidate genes in the adaptive immune system, the innate immune system has emerged as a critical avenue for research given its known link with carcinogenesis. To identify genetic markers in pathways critical to innate immunity, we conducted an association study of 551 glioma cases and 865 matched controls of European ancestry to investigate "tag" single nucleotide polymorphisms (SNP) in 148 genetic regions. Two independent U.S. case-control studies included were as follows: a hospital-based study conducted by the National Cancer Institute (263 cases, 330 controls) and a community-based study conducted by the National Institute for Occupational Safety and Health (288 cases, 535 controls). Tag SNPs (1,397) chosen on the basis of an r(2) of >0.8 and minor allele frequency of >5% in Caucasians in HapMap1 were genotyped. Glioma risk was estimated by odds ratios. Nine SNPs distributed across eight genetic regions (ALOX5, IRAK3, ITGB2, NCF2, NFKB1, SELP, SOD1, and STAT1) were associated with risk of glioma with P value of <0.01. Although these associations were no longer statistically significant after controlling for multiple comparisons, the associations were notably consistent in both studies. Region-based tests were statistically significant (P < 0.05) for SELP, SOD, and ALOX5. Analyses restricted to glioblastoma (n = 254) yielded significant associations for the SELP, DEFB126/127, SERPINI1, and LY96 genetic regions. We have identified a promising set of innate immunity-related genetic regions for further investigation.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA. rajarama@mail.nih.gov
Preetha
P
Rajaraman
Alina V
AV
Brenner
Mary Ann
MA
Butler
Sophia S
SS
Wang
Ruth M
RM
Pfeiffer
Avima M
AM
Ruder
Martha S
MS
Linet
Meredith
M
Yeager
Zhaoming
Z
Wang
Nick
N
Orr
Howard A
HA
Fine
Deukwoo
D
Kwon
Gilles
G
Thomas
Nathaniel
N
Rothman
Peter D
PD
Inskip
Stephen J
SJ
Chanock
D058927:5-Lipoxygenase-Activating Proteins; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins / Q000235:genetics; D030501:Epididymal Secretory Proteins / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics / Q000276:immunology; D005910:Glioma / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics; D016015:Logistic Models; D051218:Lymphocyte Antigen 96 / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D019255:NADPH Oxidases / Q000235:genetics; D052002:NF-kappa B p50 Subunit / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D050794:STAT1 Transcription Factor / Q000235:genetics; D051149:Selenoprotein P / Q000235:genetics; D015843:Serpins / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014481:United States; D044465:White People; D023083:beta-Defensins; D000097522:Neuroserpin
D058927:5-Lipoxygenase-Activating Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D030501:Epididymal Secretory Proteins; D053592:Interleukin-1 Receptor-Associated Kinases; D051218:Lymphocyte Antigen 96; D008565:Membrane Proteins; D009124:Muscle Proteins; D019255:NADPH Oxidases; D052002:NF-kappa B p50 Subunit; D009479:Neuropeptides; D050794:STAT1 Transcription Factor; D051149:Selenoprotein P; D015843:Serpins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D023083:beta-Defensins; D000097522:Neuroserpin; C548592:ALOX5AP protein, human; C426184:DEFB126 protein, human; C492400:ITGB1BP2 protein, human; C495377:LY96 protein, human; C489548:NFKB1 protein, human; C000606290:SOD1 protein, human; C494079:STAT1 protein, human; C527764:NCF2 protein, human; C507771:IRAK3 protein, human