title: Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population.
abstract: ABO blood serotype A is known to be associated with risk of gastric cancer (GC), but little is known how ABO alleles and the fucosyltransferase (FUT) enzymes and genes which are involved in Lewis antigen formation [and in Helicobacter pylori (H. pylori) binding and pathogenicity] may be related to GC risk in a European population. The authors conducted an investigation of 32 variants at ABO and FUT1-7 loci and GC risk in a case-control study of 365 cases and 1,284 controls nested within the EPIC cohort (the EPIC-Eurgast study). Four variants (including rs505922) in ABO, and allelic blood group A (AO+AA, odds ratio=1.84, 95%CI=1.20-2.80) were associated with diffuse-type GC; however, conditional models with other ABO variants indicated that the associations were largely due to allelic blood group A. One variant in FUT5 was also associated with diffuse-type GC, and four variants (and haplotypes) in FUT2 (Se), FUT3 (Le) and FUT6 with intestinal-type GC. Further, one variant in ABO, two in FUT3 and two in FUT6 were associated with H. pylori infection status in controls, and two of these (in FUT3 and FUT6) were weakly associated with intestinal-type GC risk. None of the individual variants surpassed a Bonferroni corrected p-value cutoff of 0.0016; however, after a gene-based permutation test, two loci [FUT3(Le)/FUT5/FUT6 and FUT2(Se)] were significantly associated with diffuse- and intestinal-type GC, respectively. Replication and functional studies are therefore recommended to clarify the role of ABO and FUT alleles in H. pylori infection and subtype-specific gastric carcinogenesis.
authors.affiliation: Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Duell
authors.forename: Catalina
authors.initials: C
authors.lastname: Bonet
authors.forename: Xavier
authors.initials: X
authors.lastname: Muñoz
authors.forename: Leila
authors.initials: L
authors.lastname: Lujan-Barroso
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Antoine
authors.initials: A
authors.lastname: Racine
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Cosmeri
authors.initials: C
authors.lastname: Rizzato
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Marcial
authors.initials: M
authors.lastname: Argüelles
authors.forename: Emilio
authors.initials: E
authors.lastname: Sánchez-Cantalejo
authors.forename: Saioa
authors.initials: S
authors.lastname: Chamosa
authors.forename: José María
authors.initials: JM
authors.lastname: Huerta
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nick
authors.initials: N
authors.lastname: Wareham
authors.forename: Rutch C
authors.initials: RC
authors.lastname: Travis
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Nikos
authors.initials: N
authors.lastname: Yiannakouris
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Bodil
authors.initials: B
authors.lastname: Ohlsson
authors.forename: Björn
authors.initials: B
authors.lastname: Lindkvist
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Johansson
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.forename: Matthias
authors.initials: M
authors.lastname: Johansson
authors.forename: Claus
authors.initials: C
authors.lastname: Fenger
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Núria
authors.initials: N
authors.lastname: Sala
authors.forename: Carlos A
authors.initials: CA
authors.lastname: González
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics*
chemical_list: D000017:ABO Blood-Group System; D005647:Fucosyltransferases
keywords: ABO; FUT; blood group; gastric cancer; genetic susceptibility