title: IL12RB2 Polymorphisms correlate with risk of lung adenocarcinoma.
abstract: In a previous study, lack of IL-12 signaling in il12rb2 knock-out mice was found to predispose to lung adenocarcinoma (LAC). We asked whether specific polymorphisms of the human IL12RB2 gene may confer susceptibility to LAC. We studied IL12RB2 single nucleotide polymorphisms (SNPs) spanning from the promoter to the first untranslated exon of the gene. Genotypes of 49 individuals with LAC were compared with those of 93 healthy subjects. Two allele variants were found to be associated with increased susceptibility to LAC. One haplotype (hap), hap18, was more frequent in patients (18%) versus controls (6%) and significantly associated with increased probability of disease occurrence. Furthermore, IL-12 driven STAT4 phosphorylation in T cell blasts from healthy individuals was found to correlate with both single allele variants and haplotypes. In conclusion, genetically determined low signaling activity of IL-12R predisposes to the development of LAC.
authors.affiliation: U.O.C. Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy. Electronic address: ignaziaprigione@gaslini.org.
authors.forename: Ignazia
authors.initials: I
authors.lastname: Prigione
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Angela Elvira
authors.initials: AE
authors.lastname: Covone
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Giacopelli
authors.affiliation: U.O.C. Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bocca
authors.affiliation: U.O.C. Immunoematologia e Medicina Trasfusionale, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Risso
authors.affiliation: U.O.C. Immunoematologia e Medicina Trasfusionale, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Gino
authors.initials: G
authors.lastname: Tripodi
authors.affiliation: U.O.S.D. Epidemiologia, Biostatistica e Comitati, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Pistorio
authors.affiliation: S.C. Genomica Tumorale, Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sozzi
authors.affiliation: U.O.C. Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Irma
authors.initials: I
authors.lastname: Airoldi
authors.affiliation: U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genova, Italy; Università degli Studi di Genova, Genova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.affiliation: U.O.C. Laboratorio di Oncologia, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000483:Alleles; D000818:Animals; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D053707:Receptors, Interleukin-12 / Q000235:genetics* / Q000276:immunology; D012306:Risk; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D020506:Untranslated Regions
chemical_list: C508439:IL12RB2 protein, human; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D020506:Untranslated Regions; D018664:Interleukin-12
keywords: Genotype–phenotype association; Lung adenocarcinoma susceptibility; STAT4 Phosphorylation