TY - JOUR
T1 - Association of JAK-STAT pathway related genes with lymphoma risk
T2 - Results of a European case-control study (EpiLymph)
AU - Butterbach, Katja
AU - Beckmann, Lars
AU - de Sanjosé, Silvia
AU - Benavente, Yolanda
AU - Becker, Nikolaus
AU - Foretova, Lenka
AU - Maynadie, Marc
AU - Cocco, Pierluigi
AU - Staines, Anthony
AU - Boffetta, Paolo
AU - Brennan, Paul
AU - Nieters, Alexandra
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - Association study
KW - Epidemiology
KW - Janus kinase-signal transducer and activator of transcription
KW - Lymphoma
KW - Susceptibility
UR - http://www.scopus.com/inward/record.url?scp=79954415963&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2011.08632.x
DO - 10.1111/j.1365-2141.2011.08632.x
M3 - Article
C2 - 21418178
AN - SCOPUS:79954415963
SN - 0007-1048
VL - 153
SP - 318
EP - 333
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 3
ER -