Association of Helicobacter pylori-related distal gastric cancer with the HLA class II gene DQB10602 and cagA strains in a southern European population.
BACKGROUND
Distinct human leukocyte antigen (HLA)-DQ genes have been associated with an increased or reduced risk for gastric cancer, but its association with Helicobacter pylori status is controversial. In the present study we evaluated the influence of host HLA DQA1 and DQB1 loci, H. pylori genotype, and socio-economic factors on predicting H. pylori-associated distal gastric cancer in a southern European population.


METHODS
In a prospective case-control (1 : 2) study, 42 patients with H. pylori-associated distal gastric cancer were matched by age (+/-5 years) and gender to 84 patients with H. pylori-associated benign gastroduodenal disease (controls). The level of education received, smoking status, alcohol consumption, origin and familial history of gastric cancer were registered at inclusion. HLA DQA1 and DQB1 typing and H. pylori genotyping were determined from endoscopic gastric mucosal biopsies.


RESULTS
Compared with control patients, a positive association with cagA(+) strains (p < .002) and a negative association with vacA-s2 strains (p < .02) was found in patients with distal gastric cancer. At the DQB1 locus, the (*)0602 allele was more frequent in distal gastric cancer than in controls (26.2% vs. 4.8%; p < .005). After correction for multiple comparisons (exact multiple regression analysis) the cagA(+) status and the DQB1(*)0602 allele were associated with an increased distal gastric cancer risk (OR 3.7; 95% CI = 1.33-12.26 and OR 4.82; 95% CI = 1.24-19.83, respectively) whereas the vacA-s2 status was associated with a decreased risk (OR 0.33; 95% CI = 0.10-0.94).


CONCLUSIONS
Our findings suggest that in the H. pylori-infected southern European population, the cagA genotype and the HLA-DQB1(*)0602 gene confer an increased risk for distal gastric cancer.
Quintero
Enrique
E
Gastroenterology Department, University Hospital of the Canary Islands, Spain. equinter@doymanet.es
Pizarro
M Angeles
MA
Rodrigo
Luis
L
Piqué
Josep M
JM
Lanas
Angel
A
Ponce
Julio
J
Miño
Gonzalo
G
Gisbert
Javier
J
Jurado
Aurora
A
Herrero
M José
MJ
Jiménez
Alejandro
A
Torrado
Julio
J
Ponte
Ana
A
Díaz-de-Rojas
Francisco
F
Salido
Eduardo
E
D000368:Aged; D000942:Antigens, Bacterial / Q000032:analysis / Q000235:genetics*; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics*; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D008562:Membrane Glycoproteins; C080866:cagA protein, Helicobacter pylori