TY - JOUR
T1 - Variation at ABO histo-blood group and FUT loci and diffuse and intestinal gastric cancer risk in a European population
AU - Duell, Eric J.
AU - Bonet, Catalina
AU - Munoz, Xavier
AU - Lujan-Barroso, Leila
AU - Weiderpass, Elisabete
AU - Boutron-Ruault, Marie-Christine
AU - Racine, Antoine
AU - Severi, Gianluca
AU - Canzian, Federico
AU - Rizzato, Cosmeri
AU - Boeing, Heiner
AU - Overvad, Kim
AU - Tjonneland, Anne
AU - Argueelles, Marcial
AU - Sanchez-Cantalejo, Emilio
AU - Chamosa, Saioa
AU - Maria Huerta, Jose
AU - Barricarte, Aurelio
AU - Khaw, Kay-Tee
AU - Wareham, Nick
AU - Travis, Rutch C.
AU - Trichopoulou, Antonia
AU - Trichopoulos, Dimitrios
AU - Yiannakouris, Nikos
AU - Palli, Domenico
AU - Agnoli, Claudia
AU - Tumino, Rosario
AU - Naccarati, Alessio
AU - Panico, Salvatore
AU - Bueno-de-Mesquita, H. B(as)
AU - Siersema, Peter D.
AU - Peeters, Petra H. M.
AU - Ohlsson, Bodil
AU - Lindkvist, Bjorn
AU - Johansson, Ingegerd
AU - Ye, Weimin
AU - Johansson, Matthias
AU - Fenger, Claus
AU - Riboli, Elio
AU - Sala, Nuria
AU - Gonzalez, Carlos A.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - gastric cancer
KW - blood group
KW - ABO
KW - FUT
KW - genetic susceptibility
U2 - 10.1002/ijc.29034
DO - 10.1002/ijc.29034
M3 - Article
C2 - 24947433
SN - 0020-7136
VL - 136
SP - 880
EP - 893
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 4
ER -
