Genetic polymorphism in chemokine CCL22 and susceptibility to Helicobacter pylori infection-related gastric carcinoma.
BACKGROUND
Gastric carcinoma is widely considered to be related to Helicobacter pylori infection, and the chemokine (C-C motif) ligand 22 (CCL22) plays an important role in suppressing immune responses against H. pylori and tumor cells. In this study, the authors examined the association between single nucleotide polymorphisms (SNPs) in the CCL22 gene and the risk of gastric carcinoma.


METHODS
Information on SNPs in the CCL22 coding region was obtained from the HapMap Project database. Genotypes were determined in a case-control cohort that consisted of 1001 patients with gastric carcinoma and 1066 controls, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed by using a logistic regression model. Serum H. pylori antibody levels were measured by using an enzyme-linked immunosorbent assay.


RESULTS
The 16C-->A SNP (reference SNP no. 4359426) in exon 1 of the CCL22 gene, which causes a 2 aspartate (2Asp) to 2 alanine (2Ala) substitution in the CCL22 protein, was associated with a significantly increased risk of gastric carcinoma. Individuals who were homozygous for the Ala/Ala genotype had an OR of 2.27 (95% CI, 1.28-4.02) compared with individuals who had the Asp/Asp genotype. Stratification analysis indicated that the association was more pronounced among men (OR, 2.64; 95% CI, 1.29-5.41) and among younger individuals (OR, 2.85; 95% CI, 1.36-5.96) compared with women and older individuals. Moreover, a multiplicative joint effect between the CCL22 SNP and H. pylori infection that intensified the risk was observed (OR for the presence of both Ala/Ala genotype and H. pylori infection, 18.37; 95% CI, 2.30-146.67).


CONCLUSIONS
The results from this study suggested that the CCL22 polymorphism is associated with an increase risk of developing H. pylori infection-related gastric carcinoma.
Wang
Guanghai
G
Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yu
Dianke
D
Tan
Wen
W
Zhao
Dan
D
Wu
Chen
C
Lin
Dongxin
D
D016022:Case-Control Studies; D054422:Chemokine CCL22 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology*
C515482:CCL22 protein, human; D054422:Chemokine CCL22