Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST).
BACKGROUND
The relative contribution to gastric cancer (GC) risk of variants in genes that determine the inflammatory response remains mostly unknown and results from genotyping studies are inconsistent.


METHODS
A nested case-control study within the prospective European Prospective Investigation into Cancer and Nutrition cohort was carried out, including 248 gastric adenocarcinomas and 770 matched controls. Twenty common polymorphisms at cytokine genes [interleukin (IL)1A, IL1B, IL1RN, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, lymphotoxin alpha and tumor necrosis factor (TNF)] were analyzed. Antibodies against Helicobacter pylori (Hp) and CagA were measured.


RESULTS
IL1RN 2R/2R genotype [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.19-4.96] and allele IL1RN Ex5-35C were associated with an increased risk of Hp(+) non-cardia GC. IL8 -251AA genotype was associated with a decreased risk of Hp(+) non-cardia GC (OR 0.51; 95% CI 0.32-0.81), mainly of the intestinal type. These associations were not modified by CagA status. Carriers of IL1B -580C and TNF -487A alleles did not associate with an increased risk. A moderately increased risk of Hp(+) non-cardia GC for IL4R -29429T variant was observed (OR 1.74; 95% CI 1.15-2.63).


CONCLUSIONS
This prospective study confirms the association of IL1RN polymorphisms with the risk of non-cardia GC and indicates that IL8 -251T>A may modify the risk for GC.
Crusius
J B A
JB
Laboratory of Immunogenetics, Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Canzian
F
F
Capellá
G
G
Peña
A S
AS
Pera
G
G
Sala
N
N
Agudo
A
A
Rico
F
F
Del Giudice
G
G
Palli
D
D
Plebani
M
M
Boeing
H
H
Bueno-de-Mesquita
H B
HB
Carneiro
F
F
Pala
V
V
Save
V E
VE
Vineis
P
P
Tumino
R
R
Panico
S
S
Berglund
G
G
Manjer
J
J
Stenling
R
R
Hallmans
G
G
Martínez
C
C
Dorronsoro
M
M
Barricarte
A
A
Navarro
C
C
Quirós
J R
JR
Allen
N
N
Key
T J
TJ
Binghan
S
S
Caldas
C
C
Linseisen
J
J
Kaaks
R
R
Overvad
K
K
Tjønneland
A
A
Büchner
F C
FC
Peeters
P H M
PH
Numans
M E
ME
Clavel-Chapelon
F
F
Trichopoulou
A
A
Lund
E
E
Jenab
M
M
Rinaldi
S
S
Ferrari
P
P
Riboli
E
E
González
C A
CA
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007378:Interleukins / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D007378:Interleukins; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha