title: The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma.
abstract: Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Carvalho
authors.forename: C
authors.initials: C
authors.lastname: Cunha
authors.forename: A J
authors.initials: AJ
authors.lastname: Almeida
authors.forename: N S
authors.initials: NS
authors.lastname: Osório
authors.forename: M
authors.initials: M
authors.lastname: Saraiva
authors.forename: M
authors.initials: M
authors.lastname: Teixeira-Coelho
authors.forename: S
authors.initials: S
authors.lastname: Pedreiro
authors.forename: E
authors.initials: E
authors.lastname: Torrado
authors.forename: N
authors.initials: N
authors.lastname: Domingues
authors.forename: A G
authors.initials: AG
authors.lastname: Gomes-Alves
authors.forename: A
authors.initials: A
authors.lastname: Marques
authors.forename: J F
authors.initials: JF
authors.lastname: Lacerda
authors.forename: M G
authors.initials: MG
authors.lastname: da Silva
authors.forename: M
authors.initials: M
authors.lastname: Gomes
authors.forename: A C
authors.initials: AC
authors.lastname: Pinto
authors.forename: F
authors.initials: F
authors.lastname: Torres
authors.forename: P
authors.initials: P
authors.lastname: Rendeiro
authors.forename: P
authors.initials: P
authors.lastname: Tavares
authors.forename: M
authors.initials: M
authors.lastname: Di Ianni
authors.forename: R
authors.initials: R
authors.lastname: Medeiros
authors.forename: P
authors.initials: P
authors.lastname: Heutink
authors.forename: P M
authors.initials: PM
authors.lastname: Bracci
authors.forename: L
authors.initials: L
authors.lastname: Conde
authors.forename: P
authors.initials: P
authors.lastname: Ludovico
authors.forename: J
authors.initials: J
authors.lastname: Pedrosa
authors.forename: P
authors.initials: P
authors.lastname: Maciel
authors.forename: L
authors.initials: L
authors.lastname: Pitzurra
authors.forename: F
authors.initials: F
authors.lastname: Aversa
authors.forename: H
authors.initials: H
authors.lastname: Marques
authors.forename: A
authors.initials: A
authors.lastname: Paiva
authors.forename: C F
authors.initials: CF
authors.lastname: Skibola
authors.forename: L
authors.initials: L
authors.lastname: Romani
authors.forename: A G
authors.initials: AG
authors.lastname: Castro
authors.forename: F
authors.initials: F
authors.lastname: Rodrigues
mesh_terms: D005260:Female; D005828:Genetics, Population; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D051217:Toll-Like Receptor 9 / Q000235:genetics*
chemical_list: C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9