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.
Wolpin
Brian M
BM
Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. bwolpin@partners.org
Kraft
Peter
P
Xu
Mousheng
M
Steplowski
Emily
E
Olsson
Martin L
ML
Arslan
Alan A
AA
Bueno-de-Mesquita
H Bas
HB
Gross
Myron
M
Helzlsouer
Kathy
K
Jacobs
Eric J
EJ
LaCroix
Andrea
A
Petersen
Gloria
G
Stolzenberg-Solomon
Rachael Z
RZ
Zheng
Wei
W
Albanes
Demetrius
D
Allen
Naomi E
NE
Amundadottir
Laufey
L
Austin
Melissa A
MA
Boutron-Ruault
Marie-Christine
MC
Buring
Julie E
JE
Canzian
Federico
F
Chanock
Stephen J
SJ
Gaziano
J Michael
JM
Giovannucci
Edward L
EL
Hallmans
Göran
G
Hankinson
Susan E
SE
Hoover
Robert N
RN
Hunter
David J
DJ
Hutchinson
Amy
A
Jacobs
Kevin B
KB
Kooperberg
Charles
C
Mendelsohn
Julie B
JB
Michaud
Dominique S
DS
Overvad
Kim
K
Patel
Alpa V
AV
Sanchéz
Maria-José
MJ
Sansbury
Leah
L
Shu
Xiao-Ou
XO
Slimani
Nadia
N
Tobias
Geoffrey S
GS
Trichopoulos
Dimitrios
D
Vineis
Paolo
P
Visvanathan
Kala
K
Virtamo
Jarmo
J
Wactawski-Wende
Jean
J
Watters
Joanne
J
Yu
Kai
K
Zeleniuch-Jacquotte
Anne
A
Hartge
Patricia
P
Fuchs
Charles S
CS
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