Variant ABO blood group alleles, secretor status, and risk of pancreatic cancer: Results from the pancreatic cancer cohort consortium

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. BuringFederico 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

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Background: Subjects with non-O ABO blood group alleles have increased risk of pancreatic cancer. Glycosyltransferase activity is greater for the A1 versus A2 variant, whereas O01 and O02 variants are nonfunctioning. We hypothesized: 1) A1 allele would confer greater risk than A2 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 A1 but not A2 alleles. Compared with subjects with genotype O/O, genotypes A2/O, A2/A 1, A1/O, and A1/A1 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, A1, and A2 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-value, O01 versus O02 = 0.94, A1 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.

Original languageEnglish (US)
Pages (from-to)3140-3149
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume19
Issue number12
DOIs
StatePublished - Dec 2010

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