title: Association of JAK-STAT pathway related genes with lymphoma risk: results of a European case-control study (EpiLymph).
abstract: Previous studies have suggested an important role for the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway in tumour development. Therefore, we explored genetic variants in JAK-STAT pathway associated genes with lymphoma risk. In samples of the EpiLymph case-control study we genotyped 1536 single nucleotide polymorphisms (SNPs) using GoldenGate BeadArray™ Technology (Illumina, San Diego, CA, USA). Here, we report the associations between selected SNPs and haplotypes of the JAK-STAT pathway and risk of Hodgkin lymphoma (HL), B-cell non-Hodgkin lymphoma (B-NHL) and most frequent B-NHL subtypes. Among 210 relevant JAK-STAT pathway-related SNPs, polymorphisms in nine genes (BMF, IFNG, IL12A, SOCS1, STAT1, STAT3, STAT5A, STAT6, TP63) were significantly associated with lymphoma risk. At a study-wise significance level, we obtained a risk reduction of 28% among carriers of the heterozygous genotype of the STAT3 variant (rs1053023) for B-NHL. For six other variants within the STAT3 gene we observed an inverse association with different lymphoma subtypes. A reduced risk for HL was observed for the heterozygous genotype of the STAT6 SNP (rs324011). This is an explorative investigation to examine associations between JAK-STAT signalling related genes and lymphoma risk. The results implicate a relevant role of certain pathway-related genes in lymphomagenesis, but still need to be approved by independent studies.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Butterbach
authors.forename: Lars
authors.initials: L
authors.lastname: Beckmann
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Benavente
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Becker
authors.forename: Lenka
authors.initials: L
authors.lastname: Foretova
authors.forename: Marc
authors.initials: M
authors.lastname: Maynadie
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Cocco
authors.forename: Anthony
authors.initials: A
authors.lastname: Staines
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nieters
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D016022:Case-Control Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006689:Hodgkin Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D053612:Janus Kinases / Q000235:genetics*; D008223:Lymphoma / Q000453:epidemiology / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000453:epidemiology / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050791:STAT Transcription Factors / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D050791:STAT Transcription Factors; D053612:Janus Kinases