title: Variations in genes involved in regulation of the nuclear factor - κB pathway and the risk of acute myeloid leukaemia.
abstract: Genes involved in regulation of the nuclear factor - kappa B (NF-κB) pathway are suggested to play a role in the pathogenesis of acute myeloid leukaemia (AML). The present study aimed to assess the association between the NF-κB1, TRAF3 and TLRs genes single nucleotide polymorphisms (SNPs) and disease susceptibility as well as progression in patients with AML. For this purpose 62 patients and 126 healthy individuals were genotyped for NF-κB1 (rs28362491), TRAF3 (rs11160707; rs12147254), TLR2 (rs201786064), TLR4 (rs4986790; rs4986791) and TLR9 (rs5743836; rs187084) alleles. Three SNPs were found to be associated with the risk for the AML development. The TRAF3 (rs12147254) AA homozygosity (RR = 2.770, P = 0.0392), TLR9 (rs5743836) C wild-type allele (RR = 2.542, P = 0.0096) as well as TLR9 (rs187084) T allele (RR = 13.396, P < 0.0001) and its homozygosity (RR = 11.805, P < 0.0001) were more frequent among patients with AML than healthy individuals. The associations of the rs187084 SNP were significant for both sexes. Moreover, patients who relapsed were more frequently characterized with the presence of the rs187084 TLR9 TT genotype (P = 0.045) or the rs12147254 TRAF3 A variant (P = 0.066). In conclusion, polymorphisms within the TLR9 and TRAF3 genes are associated with predisposition to AML and may affect the progression of the disease in the Polish population.
authors.affiliation: Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Rybka
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Gębura
authors.affiliation: Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Wróbel
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Wysoczańska
authors.affiliation: Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Stefanko
authors.affiliation: Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kuliczkowski
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.|Department of Internal Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Bogunia-Kubik
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D054643:INDEL Mutation; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016328:NF-kappa B / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics; D055815:Young Adult
chemical_list: D016328:NF-kappa B; D051193:Toll-Like Receptors