This study indicates that the LTA +252G allele is associated with increased risk for the presence of GC in a Helicobacter pylori infection positive subgroup and potential interaction between IL-10 and LTA may contribute to the risk of GC.
In the present study, it was observed that the expression of IL‑10 was significantly upregulated in gastric tumor tissues and serum samples of patients with gastric cancer.
Our findings suggest that IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872 and IL-10rs1800896 polymorphisms may serve as genetic biomarkers of gastric cancer in Asians.
This finding, taken together with previous evidence, provides a possible explanation for previous discrepant association results and supports the idea that IL10 gene polymorphisms can differentially affect GC development among populations.
The other three SNPs, the allele "C" of rs1800871 in IL10 (OR = 1.33, 95% CI = 1.04-1.90; P = 0.026 in the additive model; OR = 1.46, 95% CI = 1.04-2.06; P = 0.030 in the recessive model), the allele "A" of rs2976391 in PSCA (OR = 1.30, 95% CI = 1.01-1.66; P = 0.041 in the additive model and OR = 1.48, 95% CI = 1.04-2.11, P = 0.028 in the recessive model), and the allele "G" of rs17109928 in NOC3L gene (OR = 1.34, 95% CI = 1.01-1.78; P = 0.042 by additive model analysis; OR = 1.47, 95% CI = 1.04-2.07, P = 0.028 by dominant model analysis), showed an association with an increased risk of gastric cancer.
IFN-γ and IL-10 levels were significantly higher in early (I/II) and late stage (III/IV) gastric cancer; IL-1β and IL-8 were higher and MCP-1 was lower only in late stage (IV) patients.
Our results suggest that the HLA class II and IL-10-592A/C polymorphisms synergistically affect the susceptibility to GC development of H. pylori-infected individuals in the Japanese population.
Based on 40 studies and 18950 participants, we found the variant IL-10 -1082G allele significantly increased susceptibility to digestive cancer, especially for gastric cancer and in Asian population.
The IL-10-1082/-819/-592 genotype status and haplotype were associated with an increased risk for gastric cancer development, not peptic ulcer, in Japan.
The results suggest that this IL-10 haplotyping might be involved in development of radiation-associated gastric cancer of the diffuse type, and that IL-10 haplotypes may explain individual differences in the radiation-related risk of gastric cancer.
CONCLUSIONS Extending previous findings, we demonstrate a protective role of the IL-10 gene -819T allele in susceptibility to gastric cancer, and this role was more evident for gastric adenocarcinoma.
IL-1beta+3954_T/C (OR 2.1, 1.0-4.3), IL-1RN*2/L (OR 3.5, 1.7-7.3) and IL-10-592_C/A (OR 3.2, 1.5-6.8) were individually associated with GC, and a combination of these cytokine polymorphisms with H pylori vacA s1b and m1 further increased the risk (OR 7.2, 1.4-36.4).
The relative mRNA expression levels (RQ) of TNF-α, IL-8, and IL-10 were markedly downregulated in the CG group (median RQs = 0.128, 0.247, and 0.614, respectively), while the RQ levels of TNF-α in the GC group were upregulated (RQ = 2.749), but were basal for IL-8 (RQ = 1.053) and downregulated for IL-10 (RQ = 0.179).
In a recessive model of the IL10-819C/T polymorphism, a significantly decreased risk of GC was found compared with AG and non-cancer subjects, respectively (AG→GC: odds ratio OR 0.41; non-cancer→GC: OR 0.57).
These findings suggest that genetic polymorphisms in IL-8, IL-10 and TNFalpha may play important roles in developing gastric cancer in the Chinese population.
Our findings provided evidence for a causal role of genetically elevated IL-10 in the development of gastric cancer, especially in East Asians and for intestinal type gastric cancer.
In this article, the present author explored the roles of H. pylori infection and IL-10 promoter polymorphisms in development of gastric cancer in this area.