TY - JOUR
T1 - Variant ABO blood group alleles, secretor status, and risk of pancreatic cancer
T2 - Results from the pancreatic cancer cohort consortium
AU - Wolpin, Brian M.
AU - Kraft, Peter
AU - Xu, Mousheng
AU - Steplowski, Emily
AU - Olsson, Martin L.
AU - Arslan, Alan A.
AU - Bueno-de-Mesquita, H. Bas
AU - Gross, Myron
AU - Helzlsouer, Kathy
AU - Jacobs, Eric J.
AU - LaCroix, Andrea
AU - Petersen, Gloria
AU - Stolzenberg-Solomon, Rachael Z.
AU - Zheng, Wei
AU - Albanes, Demetrius
AU - Allen, Naomi E.
AU - Amundadottir, Laufey
AU - Austin, Melissa A.
AU - Boutron-Ruault, Marie Christine
AU - Buring, Julie E.
AU - Canzian, Federico
AU - Chanock, Stephen J.
AU - Gaziano, J. Michael
AU - Giovannucci, Edward L.
AU - Hallmans, Göran
AU - Hankinson, Susan E.
AU - Hoover, Robert N.
AU - Hunter, David J.
AU - Hutchinson, Amy
AU - Jacobs, Kevin B.
AU - Kooperberg, Charles
AU - Mendelsohn, Julie B.
AU - Michaud, Dominique S.
AU - Overvad, Kim
AU - Patel, Alpa V.
AU - Sanchéz, Maria José
AU - Sansbury, Leah
AU - Shu, Xiao Ou
AU - Slimani, Nadia
AU - Tobias, Geoffrey S.
AU - Trichopoulos, Dimitrios
AU - Vineis, Paolo
AU - Visvanathan, Kala
AU - Virtamo, Jarmo
AU - Wactawski-Wende, Jean
AU - Watters, Joanne
AU - Yu, Kai
AU - Zeleniuch-Jacquotte, Anne
AU - Hartge, Patricia
AU - Fuchs, Charles S.
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
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U2 - 10.1158/1055-9965.EPI-10-0751
DO - 10.1158/1055-9965.EPI-10-0751
M3 - Article
C2 - 20971884
AN - SCOPUS:78650323492
SN - 1055-9965
VL - 19
SP - 3140
EP - 3149
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 12
ER -