title: An international case-control study of interleukin-4Ralpha, interleukin-13, and cyclooxygenase-2 polymorphisms and glioblastoma risk.
abstract: Previous studies found that allergies are inversely related to risk of glioma. In an earlier publication, using data from a Swedish case-control study, Schwartzbaum et al. report an inverse relation between risk of glioblastoma and four single nucleotide polymorphisms (SNP) on two genes [interleukin (IL)-4Ralpha, IL-13] that are associated with allergies. In addition, recent studies suggest that IL-4 and IL-13 induce cyclooxygenase-2 (COX-2) to resolve brain inflammation. To see whether previous Swedish results (110 cases, 430 controls) would be replicated, we estimated the association between glioblastoma and two IL-4Ralpha (rs1805015, rs1801275) and two IL-13 (rs20541, rs1800925) SNPs and their haplotypes and one COX-2 SNP (-765GC) using additional English, Danish, and Finnish data (217 cases, 1,171 controls). Among general population controls, we evaluated associations between these haplotypes, the COX-2 SNP, and self-reported allergies. Our data did not support our original observations relating individual IL-4Ralpha, IL-13, or COX-2 SNPs to glioblastoma risk. However, the T-G IL-4Ralpha haplotype was associated with glioblastoma risk (odds ratio, 2.26; 95% confidence interval, 1.13-4.52) and there was a suggestion of an inverse relation between this haplotype and hayfever prevalence among controls (odds ratio, 0.38; 95% confidence interval, 0.14-1.03). The lack of support for a link between four IL-4Ralpha and IL-13 SNPs and glioblastoma may reflect the absence of associations or may result from uncontrolled confounding by haplotypes related both to those that we examined and glioblastoma. Nonetheless, the association between the T-G IL-4Ralpha haplotype and glioblastoma risk may indicate a role of immune factors in glioblastoma development.
authors.affiliation: Division of Epidemiology, School of Public Health, Ohio State University, Starling-Loving Hall, 320 West Tenth Avenue, Columbus, OH 43210, USA. schwartzbaum.1@osu.edu
authors.forename: Judith A
authors.initials: JA
authors.lastname: Schwartzbaum
authors.forename: Anders
authors.initials: A
authors.lastname: Ahlbom
authors.forename: Stefan
authors.initials: S
authors.lastname: Lönn
authors.forename: Beatrice
authors.initials: B
authors.lastname: Malmer
authors.forename: Annette
authors.initials: A
authors.lastname: Wigertz
authors.forename: Anssi
authors.initials: A
authors.lastname: Auvinen
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Brookes
authors.forename: Helle
authors.initials: H
authors.lastname: Collatz Christensen
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johansen
authors.forename: Tina
authors.initials: T
authors.lastname: Salminen
authors.forename: Minouk J
authors.initials: MJ
authors.lastname: Schoemaker
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Swerdlow
authors.forename: Waldemar
authors.initials: W
authors.lastname: Debinski
authors.forename: Maria
authors.initials: M
authors.lastname: Feychting
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000097:blood / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D006967:Hypersensitivity / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D018793:Interleukin-13 / Q000097:blood / Q000235:genetics*; D053662:Interleukin-4 Receptor alpha Subunit / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D051546:Cyclooxygenase 2