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Variant ABO Blood Group Alleles, Secretor Status, and Risk of Pancreatic Cancer: Results from the Pancreatic Cancer Cohort Consortium

Wolpin, Brian M.; Kraft, Peter; Xu, Mousheng; Steplowski, Emily; Olsson, Martin L LU ; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy and Jacobs, Eric J., et al. (2010) In Cancer Epidemiology Biomarkers & Prevention 19(12). p.3140-3149
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... (More)
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-value, 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. Cancer Epidemiol Biomarkers Prev; 19(12); 3140-9. (C) 2010 AACR. (Less)
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Cancer Epidemiology Biomarkers & Prevention
volume
19
issue
12
pages
3140 - 3149
publisher
American Association for Cancer Research
external identifiers
  • wos:000285285900015
  • scopus:78650323492
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-10-0751
language
English
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yes
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79d83fda-cdb9-4036-9f3b-69ae0cee956c (old id 1772765)
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2011-02-02 15:23:22
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@article{79d83fda-cdb9-4036-9f3b-69ae0cee956c,
  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-value, 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. Cancer Epidemiol Biomarkers Prev; 19(12); 3140-9. (C) 2010 AACR.},
  author       = {Wolpin, Brian M. and Kraft, Peter and Xu, Mousheng and Steplowski, Emily and Olsson, Martin L and Arslan, Alan A. and Bueno-de-Mesquita, H. Bas and Gross, Myron and Helzlsouer, Kathy and Jacobs, Eric J. and LaCroix, Andrea and Petersen, Gloria and Stolzenberg-Solomon, Rachael Z. and Zheng, Wei and Albanes, Demetrius and Allen, Naomi E. and Amundadottir, Laufey and Austin, Melissa A. and Boutron-Ruault, Marie-Christine and Buring, Julie E. and Canzian, Federico and Chanock, Stephen J. and Gaziano, J. Michael and Giovannucci, Edward L. and Hallmans, Goeran and Hankinson, Susan E. and Hoover, Robert N. and Hunter, David J. and Hutchinson, Amy and Jacobs, Kevin B. and Kooperberg, Charles and Mendelsohn, Julie B. and Michaud, Dominique S. and Overvad, Kim and Patel, Alpa V. and Sanchez, Maria-Jose and Sansbury, Leah and Shu, Xiao-Ou and Slimani, Nadia and Tobias, Geoffrey S. and Trichopoulos, Dimitrios and Vineis, Paolo and Visvanathan, Kala and Virtamo, Jarmo and Wactawski-Wende, Jean and Watters, Joanne and Yu, Kai and Zeleniuch-Jacquotte, Anne and Hartge, Patricia and Fuchs, Charles S.},
  issn         = {1538-7755},
  language     = {eng},
  number       = {12},
  pages        = {3140--3149},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Variant ABO Blood Group Alleles, Secretor Status, and Risk of Pancreatic Cancer: Results from the Pancreatic Cancer Cohort Consortium},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-10-0751},
  volume       = {19},
  year         = {2010},
}