Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 153, Issue 3, Pages 318-333Publisher
WILEY
DOI: 10.1111/j.1365-2141.2011.08632.x
Keywords
lymphoma; susceptibility; janus kinase-signal transducer and activator of transcription; epidemiology; association study
Categories
Funding
- German Jose Carreras Leukaemia Foundation [DJCLS_R04/08]
- EC [QLK4-CT-2000-00422, FP6-2003-FOOD-2-B]
- Federal Office for Radiation Protection (Germany) [StSch4261, StSch4420]
- Spanish Ministry of Health (Spain) [06/02/0073, FIS 08-1555 1, 051210]
- La Fondation de France
- Compagnia di San Paolo di Torino
- German Research Foundation
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P>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 (TM) 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.
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