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

Duell, Eric J.; Bonet, Catalina; Munoz, Xavier; Lujan-Barroso, Leila; Weiderpass, Elisabete; Boutron-Ruault, Marie-Christine; Racine, Antoine; Severi, Gianluca; Canzian, Federico and Rizzato, Cosmeri, et al. (2015) In International Journal of Cancer 136(4). p.880-893
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... (More)
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. What's New? Blood type A indicates a higher risk of gastric cancer, but why? This study examined the relationship between blood group genes and cancer. The authors investigated 32 variants among not only the ABO alleles, but also including the genes involved in producing the Lewis blood group antigens. They confirmed blood group A as a risk factor for diffuse-type gastric cancer, and also detected an association between certain Lewis antigen alleles and intestinal-type gastric cancer. Interestingly, these alleles also popped up among controls who harbored H. pylori infection. These associations certainly warrant further investigation into their role in gastric cancer. (Less)
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keywords
gastric cancer, blood group, ABO, FUT, genetic susceptibility
in
International Journal of Cancer
volume
136
issue
4
pages
880 - 893
publisher
John Wiley & Sons
external identifiers
  • wos:000346089900035
  • scopus:84918818967
ISSN
0020-7136
DOI
10.1002/ijc.29034
language
English
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yes
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0859d1ef-21ba-4256-b8ce-8fd28d02f727 (old id 4950671)
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2015-02-03 07:05:34
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@article{0859d1ef-21ba-4256-b8ce-8fd28d02f727,
  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. What's New? Blood type A indicates a higher risk of gastric cancer, but why? This study examined the relationship between blood group genes and cancer. The authors investigated 32 variants among not only the ABO alleles, but also including the genes involved in producing the Lewis blood group antigens. They confirmed blood group A as a risk factor for diffuse-type gastric cancer, and also detected an association between certain Lewis antigen alleles and intestinal-type gastric cancer. Interestingly, these alleles also popped up among controls who harbored H. pylori infection. These associations certainly warrant further investigation into their role in gastric cancer.},
  author       = {Duell, Eric J. and Bonet, Catalina and Munoz, Xavier and Lujan-Barroso, Leila and Weiderpass, Elisabete and Boutron-Ruault, Marie-Christine and Racine, Antoine and Severi, Gianluca and Canzian, Federico and Rizzato, Cosmeri and Boeing, Heiner and Overvad, Kim and Tjonneland, Anne and Argueelles, Marcial and Sanchez-Cantalejo, Emilio and Chamosa, Saioa and Maria Huerta, Jose and Barricarte, Aurelio and Khaw, Kay-Tee and Wareham, Nick and Travis, Rutch C. and Trichopoulou, Antonia and Trichopoulos, Dimitrios and Yiannakouris, Nikos and Palli, Domenico and Agnoli, Claudia and Tumino, Rosario and Naccarati, Alessio and Panico, Salvatore and Bueno-de-Mesquita, H. B(as) and Siersema, Peter D. and Peeters, Petra H. M. and Ohlsson, Bodil and Lindkvist, Bjorn and Johansson, Ingegerd and Ye, Weimin and Johansson, Matthias and Fenger, Claus and Riboli, Elio and Sala, Nuria and Gonzalez, Carlos A.},
  issn         = {0020-7136},
  keyword      = {gastric cancer,blood group,ABO,FUT,genetic susceptibility},
  language     = {eng},
  number       = {4},
  pages        = {880--893},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population},
  url          = {http://dx.doi.org/10.1002/ijc.29034},
  volume       = {136},
  year         = {2015},
}