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


CONCLUSIONS
These data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk rather than actions of other nearby genes on chromosome 9q34.
Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. bwolpin@partners.org
Brian M
BM
Wolpin
Peter
P
Kraft
Mousheng
M
Xu
Emily
E
Steplowski
Martin L
ML
Olsson
Alan A
AA
Arslan
H Bas
HB
Bueno-de-Mesquita
Myron
M
Gross
Kathy
K
Helzlsouer
Eric J
EJ
Jacobs
Andrea
A
LaCroix
Gloria
G
Petersen
Rachael Z
RZ
Stolzenberg-Solomon
Wei
W
Zheng
Demetrius
D
Albanes
Naomi E
NE
Allen
Laufey
L
Amundadottir
Melissa A
MA
Austin
Marie-Christine
MC
Boutron-Ruault
Julie E
JE
Buring
Federico
F
Canzian
Stephen J
SJ
Chanock
J Michael
JM
Gaziano
Edward L
EL
Giovannucci
Göran
G
Hallmans
Susan E
SE
Hankinson
Robert N
RN
Hoover
David J
DJ
Hunter
Amy
A
Hutchinson
Kevin B
KB
Jacobs
Charles
C
Kooperberg
Julie B
JB
Mendelsohn
Dominique S
DS
Michaud
Kim
K
Overvad
Alpa V
AV
Patel
Maria-José
MJ
Sanchéz
Leah
L
Sansbury
Xiao-Ou
XO
Shu
Nadia
N
Slimani
Geoffrey S
GS
Tobias
Dimitrios
D
Trichopoulos
Paolo
P
Vineis
Kala
K
Visvanathan
Jarmo
J
Virtamo
Jean
J
Wactawski-Wende
Joanne
J
Watters
Kai
K
Yu
Anne
A
Zeleniuch-Jacquotte
Patricia
P
Hartge
Charles S
CS
Fuchs
D000017:ABO Blood-Group System / Q000235:genetics*; D000483:Alleles; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D016695:Glycosyltransferases / Q000235:genetics; D006801:Humans; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D000017:ABO Blood-Group System; D016695:Glycosyltransferases