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Variation at ABO histo‐blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population
Author(s) -
Duell Eric J.,
Bonet Catalina,
Muñoz Xavier,
LujanBarroso Leila,
Weiderpass Elisabete,
BoutronRuault MarieChristine,
Racine Antoine,
Severi Gianluca,
Canzian Federico,
Rizzato Cosmeri,
Boeing Heiner,
Overvad Kim,
Tjønneland Anne,
Argüelles Marcial,
SánchezCantalejo Emilio,
Chamosa Saioa,
Huerta José María,
Barricarte Aurelio,
Khaw KayTee,
Wareham Nick,
Travis Rutch C.,
Trichopoulou Antonia,
Trichopoulos Dimitrios,
Yiannakouris Nikos,
Palli Domenico,
Agnoli Claudia,
Tumino Rosario,
Naccarati Alessio,
Panico Salvatore,
BuenodeMesquita H Bas,
Siersema Peter D.,
Peeters Petra H.M.,
Ohlsson Bodil,
Lindkvist Björn,
Johansson Ingegerd,
Ye Weimin,
Johansson Matthias,
Fenger Claus,
Riboli Elio,
Sala Núria,
González Carlos A.
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29034
Subject(s) - abo blood group system , blood type (non human) , odds ratio , biology , allele , population , haplotype , gastroenterology , medicine , genetics , gene , environmental health
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.