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

Katja Butterbach (1) , Lars Beckmann (2) , Silvia de Sanjosé (3, 4) , Yolanda Benavente (3, 4) , Nikolaus Becker (2) , Lenka Foretova (5) , Marc Maynadié (5) , Pierluigi Cocco (6) , Anthony Staines (7) , Paolo Boffetta (8, 9) , Paul Brennan (10) , Alexandra Nieters (11, 12)

1 Division of Cancer Epidemiology
2 Division of Cancer Epidemiology
3 of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme
4 CIBER de Epidemiología y Salud Ambiental
5 Cancer Epidemiology and Genetics
6 Institute of Occupational Medicine
7 School of Nursing
8 The Tisch Cancer Institute
9 IPRI - International Prevention Research Institute
10 IACR - International Agency for Cancer Research
11 Molecular Epidemiology
12 Institute for Medical Biostatistics and Medical Informatics

Previous studies have suggested an important role of the 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 BeadArrayTM Technology (Illumina, San Diego, CA). Here, we report the associations between selected SNPs and haplotypes of the JAK-STAT pathway and risk of Hodgkin lymphoma (HL), B-cell 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 the lymphomagenesis, but still need to be approved by independent studies.

Mots clés: Medicine

Katja Butterbach, Lars Beckmann, Silvia de Sanjosé, Yolanda Benavente, Nikolaus Becker, et al.. Association of JAK-STAT pathway related genes with lymphoma risk: results of a European case-control study (EpiLymph). British Journal of Haematology, 2011, 153 (3), pp.318. ⟨10.1111/j.1365-2141.2011.08632.x⟩. ⟨hal-00625170⟩