title: Genetic variants in the IL1A gene region contribute to intestinal-type gastric carcinoma susceptibility in European populations.
abstract: The most studied genetic susceptibility factors involved in gastric carcinoma (GC) risk are polymorphisms in the inflammation-linked genes interleukin 1 (IL1) B and IL1RN. Despite the evidence pointing to the IL1 region, definite functional variants reproducible across populations of different genetic background have not been discovered so far. A high density linkage disequilibrium (LD) map of the IL1 gene cluster was established using HapMap to identify haplotype tagSNPs. Eighty-seven SNPs were genotyped in a Portuguese case-control study (358 cases, 1,485 controls) for the discovery analysis. A replication study, including a subset of those tagSNPs (43), was performed in an independent analysis (EPIC-EurGast) containing individuals from 10 European countries (365 cases, 1284 controls). Single SNP and haplotype block associations were determined for GC overall and anatomopathological subtypes. The most robust association was observed for SNP rs17042407, 16Kb upstream of the IL1A gene. Although several other SNP associations were observed, only the inverse association of rs17042407 allele C with GC of the intestinal type was observed in both studies, retaining significance after multiple testing correction (p = 0.0042) in the combined analysis. The haplotype analysis of the IL1A LD block in the combined dataset revealed the association between a common haplotype carrying the rs17042407 variant and GC, particularly of the intestinal type (p = 3.1 × 10(-5) ) and non cardia localisation (p = 4.6 × 10(-3) ). These results confirm the association of IL1 gene variants with GC and reveal a novel SNP and haplotypes in the IL1A region associated with intestinal type GC in European populations.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Cecília
authors.initials: C
authors.lastname: Durães
authors.forename: Xavier
authors.initials: X
authors.lastname: Muñoz
authors.forename: Catalina
authors.initials: C
authors.lastname: Bonet
authors.forename: Nadia
authors.initials: N
authors.lastname: García
authors.forename: Adoración
authors.initials: A
authors.lastname: Venceslá
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.forename: Bárbara
authors.initials: B
authors.lastname: Peleteiro
authors.forename: Nuno
authors.initials: N
authors.lastname: Lunet
authors.forename: Henrique
authors.initials: H
authors.lastname: Barros
authors.forename: Björn
authors.initials: B
authors.lastname: Lindkvist
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Cosmeri
authors.initials: C
authors.lastname: Rizzato
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.forename: Allessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Aurelio Barricarte
authors.initials: AB
authors.lastname: Gurrea
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Céu
authors.initials: C
authors.lastname: Figueiredo
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: González
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellà
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Machado
authors.forename: Núria
authors.initials: N
authors.lastname: Sala
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C508584:IL1A protein, human; D053582:Interleukin-1alpha
keywords: IL1 gene cluster; IL1A; gastric carcinoma; genetic susceptibility; haplotypes; intestinal-type gastric carcinoma