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.
European Commission (DG-SANCO); International Agency for Research on Cancer; Health Research Fund (FIS) of the Spanish Ministry of Health [Exp PI07/0130, Exp PI12/01187, RTICC-RD12/0036/0018, RTICC-RD06/10091]; La Caixa [BM 06-130]; Regional Governments of Andalucia, Asturias, Basque Country, Murcia, Navarra ; Catalan Institute of Oncology (Spain); Danish Cancer Society (Denmark), Ligue Contre le Cancer; Institut Gustave Roussy; Mutuelle Generale de l'Education Nationale; Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe; Deutsches Krebsforschungszentrum; Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC); National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands); Norwegian Cancer Society; European Research Council (Norway); Swedish Cancer Society; Swedish Scientific Council and Regional Government; Swedish Scientific Council and Regional Government of Skane and Va asterbotten (Sweden); Cancer Research UK; Medical Research Council (United Kingdom) 2 24947433
- gastric cancer blood group ABO FUT genetic susceptibility HELICOBACTER-PYLORI INFECTION ANTIGEN-BINDING ADHESIN GENOME-WIDE ASSOCIATION PANCREATIC-CANCER COHORT CONSORTIUM LEWIS ANTIGENS GROUP ALLELES EXPRESSION VITAMIN-B-12 METAANALYSIS