Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population

Eric J. Duell, Catalina Bonet, Xavier Muñoz, Leila Lujan-Barroso, Elisabete Weiderpass, Marie Christine Boutron-Ruault, Antoine Racine, Gianluca Severi, Federico Canzian, Cosmeri Rizzato, Heiner Boeing, Kim Overvad, Anne Tjønneland, Marcial Argüelles, Emilio Sáanchez-Cantalejo, Saioa Chamosa, Josée Maríia Huerta, Aurelio Barricarte, Kay Tee Khaw, Nick WarehamRutch C. Travis, Antonia Trichopoulou, Dimitrios Trichopoulos, Nikos Yiannakouris, Domenico Palli, Claudia Agnoli, Rosario Tumino, Alessio Naccarati, Salvatore Panico, H. B. Bueno-De-Mesquita, Peter D. Siersema, Petra H M Peeters, Bodil Ohlsson, Björn Lindkvist, Ingegerd Johansson, Weimin Ye, Matthias Johansson, Claus Fenger, Elio Riboli, Núria Sala, Carlos A. González

Research output: Contribution to journalArticlepeer-review

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 (AO1AA, odds ratio51.84, 95%CI51.20-2.80) 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.

Original languageEnglish
Pages (from-to)880-893
Number of pages14
JournalInternational Journal of Cancer
Volume136
Issue number4
DOIs
Publication statusPublished - Feb 15 2015

Keywords

  • ABO
  • Blood group
  • FUT
  • Gastric cancer
  • Genetic susceptibility

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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