Association of JAK-STAT pathway related genes with lymphoma risk: results of a European case-control study (EpiLymph)

Br J Haematol. 2011 May;153(3):318-33. doi: 10.1111/j.1365-2141.2011.08632.x. Epub 2011 Mar 21.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Case-Control Studies
  • Europe / epidemiology
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Hodgkin Disease / epidemiology
  • Hodgkin Disease / genetics
  • Humans
  • Janus Kinases / genetics*
  • Lymphoma / epidemiology
  • Lymphoma / genetics*
  • Lymphoma, B-Cell / epidemiology
  • Lymphoma, B-Cell / genetics
  • Lymphoma, T-Cell / epidemiology
  • Lymphoma, T-Cell / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • STAT Transcription Factors / genetics*
  • Signal Transduction / genetics

Substances

  • STAT Transcription Factors
  • Janus Kinases