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

International Journal of Cancer, Wiley, ISSN 0020-7136

Volume 136, 4, 2015

DOI:10.1002/ijc.29034, Dimensions: pub.1034539163, PMID: 24947433,



  1. (1) Unit of Nutrition; Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL); Barcelona Spain
  2. (2) Cancer Registry of Norway, grid.418941.1
  3. (3) Department of Community Medicine, Faculty of Health Sciences; UiT The Arctic University of Norway; Tromsø Norway
  4. (4) Department of Research; Cancer Registry of Norway; Oslo Norway
  5. (5) Folkhälsans Forskningscentrum, grid.428673.c
  6. (6) Karolinska Institute, grid.4714.6
  7. (7) IGR, F‐94805 Villejuif France
  8. (8) Inserm, Centre for research in Epidemiology and Population Health (CESP); U1018, Nutrition, Hormones and Women's Health team; F-94805 Villejuif France
  9. (9) University of Paris-Sud, grid.5842.b
  10. (10) Cancer Council Victoria, grid.3263.4
  11. (11) University of Melbourne, grid.1008.9
  12. (12) Genomic Epidemiology Group, German Cancer Research Center (DKFZ); Heidelberg Germany
  13. (13) Department of Epidemiology; German Institute of Human Nutrition, Potsdam-Rehbruecke; Nuthetal Germany
  14. (14) Aarhus University, grid.7048.b, AU
  15. (15) Danish Cancer Society Research Center, Institute of Cancer Epidemiology, Diet, Cancer and Health; Copenhagen Denmark
  16. (16) Public Health Directorate; Asturias Spain
  17. (17) Andalusian School of Public Health, grid.413740.5
  18. (18) Instituto de Investigación Biosanitaria, grid.507088.2
  19. (19) Institute of Health Carlos III, grid.413448.e
  20. (20) Public Health Division of Gipuzkoa, BioDonostia Research Institute; San Sebastian Spain
  21. (21) Department of Epidemiology; Murcia Regional Health Council; Murcia Spain
  22. (22) Instituto de Salud Pública de Navarra, grid.419126.9
  23. (23) University of Cambridge, grid.5335.0
  24. (24) MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom
  25. (25) University of Oxford, grid.4991.5
  26. (26) Bureau of Epidemiologic Research, Academy of Athens; Greece
  27. (27) Hellenic Health Foundation, grid.424637.0
  28. (28) Department of Epidemiology; Harvard School of Public Health; Boston MA
  29. (29) Harokopio University, grid.15823.3d
  30. (30) Istituto per lo Studio e la Prevenzione Oncologica, grid.417623.5
  31. (31) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  32. (32) Cancer Registry and Histopathology Unit, “Civic - M.P. Arezzo” Hospital; ASP Ragusa Italy
  33. (33) Human Genetics Foundation, grid.428948.b
  34. (34) University of Naples Federico II, grid.4691.a
  35. (35) National Institute for Public Health and the Environment, grid.31147.30
  36. (36) The School of Public Health, Imperial College London; London United Kingdom
  37. (37) Department of Gastroenterology and Hepatology; University Medical Centre; Utrecht The Netherlands
  38. (38) Department of Epidemiology & Biostatistics; School of Public Health, Imperial College London; London United Kingdom
  39. (39) Julius Center for Health Sciences and Primary Care; University Medical Center; Utrecht The Netherlands
  40. (40) Skåne University Hospital, grid.411843.b
  41. (41) University of Gothenburg, grid.8761.8
  42. (42) Umeå University, grid.12650.30
  43. (43) International Agency For Research On Cancer, grid.17703.32
  44. (44) Odense University Hospital, grid.7143.1, Southern Denmark Region
  45. (45) Department of Epidemiology and Biostatistics, School of Public Health; Imperial College London; London United Kingdom


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.


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