Gastric cancer susceptibility is not linked to pro-and anti-inflammatory cytokine gene polymorphisms in whites: a Nationwide Multicenter Study in Spain.
OBJECTIVE
Recent studies have reported an association between cytokine gene polymorphisms and GC risk. However, results are inconsistent among studies from different geographic regions and ethnic groups. Our goal was to evaluate the influence of Helicobacter pylori (H. pylori) infection and host genetic factors on GC susceptibility in a population of Spanish white GC patients.


METHODS
DNA from 404 unrelated patients with GC and 404 sex- and age-matched healthy controls was typed for several functional polymorphisms in pro- (IL-1B, TNFA, LTA, IL-12p40) and anti-inflammatory (IL-4, IL-1RN, IL-10, TGFB1) genes by PCR, RFLP, and TaqMan assays. H. pylori infection and CagA/VacA antibody status were also determined by western blot serology.


RESULTS
Logistic regression analysis identified H. pylori infection with cagA strains (OR 2.54, 95% CI 1.77-3.66), smoking habit (OR 1.91, 95% CI 1.25-2.93), and positive family history of GC (OR 3.67, 95% CI 2.01-6.71) as independent risk factors for GC. None of the cytokine gene polymorphisms analyzed in this study were associated with susceptibility to GC development, whether GC patients were analyzed as a group or categorized according to anatomic location or histological subtype. Some simultaneous combinations of proinflammatory genotypes reportedly associated with greater GC risk yielded no significant differences between patients and controls.


CONCLUSIONS
Our results show that, at least in some white populations, the contribution of the cytokine gene polymorphisms evaluated in this study (IL-1B, IL-1RN, IL-12p40, LTA, IL-10, IL-4, and TGF-B1) to GC susceptibility may be less relevant than previously reported.
García-González
María Asunción
MA
Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain.
Lanas
Angel
A
Quintero
Enrique
E
Nicolás
David
D
Parra-Blanco
Adolfo
A
Strunk
Mark
M
Benito
Rafael
R
Angel Simón
Miguel
M
Santolaria
Santos
S
Sopeña
Federico
F
Piazuelo
Elena
E
Jiménez
Pilar
P
Pascual
Cristina
C
Mas
Eva
E
Irún
Pilar
P
Espinel
Jesús
J
Campo
Rafael
R
Manzano
Marisa
M
Geijo
Fernando
F
Pellisé
Maria
M
González-Huix
Ferrán
F
Nieto
Miguel
M
Espinós
Jorge
J
Titó
Llúcia
L
Bujanda
Luis
L
Zaballa
Manuel
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000032:analysis; D001426:Bacterial Proteins / Q000032:analysis; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D016481:Helicobacter Infections / Q000150:complications / Q000175:diagnosis; D016480:Helicobacter pylori / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013030:Spain; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D044465:White People
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori