Variant ABO Blood Group Alleles, Secretor Status, and Risk of Pancreatic Cancer: Results from the Pancreatic Cancer Cohort Consortium
Year: 2010
Type: article
Abstract: BACKGROUND: Subjects with non-O ABO blood group alleles have increased risk of pancreatic cancer. Glycosyltransferase activity is greater for the A(1) versus A(2) variant, whereas O01 and O02 variants are nonfunctioning. We hypothesized: 1) A(1) allele would confer greater risk than A(2) allele, 2) protective effect of the O allele would be equivalent for O01 and O02 variants, 3) secretor phenotype would modify the association with risk. METHODS: We determined ABO variants and secretor phenotype from single nucleotide polymorphisms in ABO and FUT2 genes in 1,533 cases and 1,582 controls from 12 prospective cohort studies. Adjusted odds ratios (OR) for pancreatic cancer were calculated using logistic regression. RESULTS: An increased risk was observed in participants with A(1) but not A(2) alleles. Compared with subjects with genotype O/O, genotypes A(2)/O, A(2)/A(1), A(1)/O, and A(1)/A(1) had ORs of 0.96 (95% CI, 0.72-1.26), 1.46 (95% CI, 0.98-2.17), 1.48 (95% CI, 1.23-1.78), and 1.71 (95% CI, 1.18-2.47). Risk was similar for O01 and O02 variant O alleles. Compared with O01/O01, the ORs for each additional allele of O02, A(1), and A(2) were 1.00 (95% CI, 0.87-1.14), 1.38 (95% CI, 1.20-1.58), and 0.96 (95% CI, 0.77-1.20); P, O01 versus O02 = 0.94, A(1) versus A(2) = 0.004. Secretor phenotype was not an effect modifier (P-interaction = 0.63). CONCLUSIONS: Among participants in a large prospective cohort consortium, ABO allele subtypes corresponding to increased glycosyltransferase activity were associated with increased pancreatic cancer risk. IMPACT: These data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk rather than actions of other nearby genes on chromosome 9q34.
Authors: Brian M. Wolpin, Peter Kraft, Mousheng Xu, Emily Steplowski, Martin L. Olsson, Alan A. Arslan, H. Bas Bueno-de-Mesquita, Myron Gross, Kathy Helzlsouer, Eric J. Jacobs, Andrea LaCroix, Gloria Petersen, Rachael Z. Stolzenberg-Solomon, Wei Zheng, Demetrius Albanes, Naomi E. Allen, Laufey Amundadottir, Melissa A. Austin, Marie-Christine Boutron-Ruault, Julie E. Buring, Federico Canzian, Stephen J. Chanock, J. Michael Gaziano, Edward L. Giovannucci, Göran Hallmans, Susan E. Hankinson, Robert N. Hoover, David J. Hunter, Amy Hutchinson, Kevin B. Jacobs, Charles Kooperberg, Julie B. Mendelsohn, Dominique S. Michaud, Kim Overvad, Alpa V. Patel, Maria-José Sanchéz, Leah Sansbury, Xiao-Ou Shu, Nadia Slimani, Geoffrey S. Tobias, Dimitrios Trichopoulos, Paolo Vineis, Kala Visvanathan, Jarmo Virtamo, Jean Wactawski-Wende, Joanne Watters, Kai Yu, Anne Zeleniuch-Jacquotte, Patricia Hartge, Charles S. Fuchs
Institutions: Brigham and Women's Hospital, Harvard University, Lund University, University Medical Center Utrecht, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center, New York University, Mayo Clinic, Inserm, Science Applications International Corporation (United States), Imperial College London, Academy of Athens
Language: English
Topic: Blood groups and transfusion
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1011819373, G1060151506, Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer, G1168185457, G1294540475, G1327305488, G1423636853, G1553865127, G1638177084, DNA Repair, Skin Cancer and Overall Cancer Risk, G1732728960, G1734361364, Prospective Cohort Collaborative in Pancreatic Cancer Epidemiology & Pathogenesis, G1828895303, G1963369394, G2099427675, G2145550945, G216524704, G2176833112, G2742033589, G2802736426, G2868073770, G386607036, Dietary and Hormonal Determinants of Cancer in Women, Vitamin D, Related Genes and Breast Cancer Risk, G4225032190, G443405440, G4484576498, G4522543292, G4582778782, G4847987001, G5026349245, G5108308032, G519175825, G5209003178, Physicians' Health Study II: Prevention Trial of Vitamins, G5684079324, G5881391427, G5888954722, G6124801312, G630576673, TRIAL OF ASPIRIN AND BETA-CAROTENE IN U S MD'S, G6604908402, G7238814555, G8178424689, G8399797517, G8554986239, G8750984004, G885693336, G9000072420
OpenAlex ID: W2103374690