Association between pro-(IL-8) and anti-inflammatory (IL-10) cytokine variants and their serum levels and H. pylori-related gastric carcinogenesis in northern India

Abstract

Background

Interleukin (IL)-8 -251 T/A and IL-10 (-1082 G/A and -819/592 C/T) polymorphisms and their expression may influence gastritis, atrophy, intestinal metaplasia (IM) and gastric cancer (GC) following H. pylori infection.

Methods

Genotyping of these genes was performed (ASO-PCR) in 200, 182 and 250 with GC, functional dyspepsia (FD) and healthy controls (HC), respectively. Anti- H. pylori IgG-antibody was tested in all and serums IL-8 and IL-10 were measured randomly in 60 subjects of each group by ELISA.

Results

Pro-(IL-8)-251 AA and anti-inflammatory (IL-10)-819 TT genotypes were commoner among GC than HC (p = 0.023, OR 1.86 [1.09–3.2] and p = 0.020, OR 2.0 [1.11–3.5]) but comparable with FD. IL-8 AA and IL-10-819 T allele carriage was also commoner in H. pylori-infected GC than HC (p = 0.011, OR 2.47 [1.23–5.0], and p = 0.018, OR 2.3 (1.16–4.59). IL-10-1082 G/A genotype and haplotypes (ACC, GCC, ATA and GTA) were comparable in all groups. Circulating levels of IL-8 and IL-10 were higher among GC than HC but comparable to FD (IL-8; 57.64 [6.44–319.46] vs. 54.35 [4.24–318.96] and 26.33 [4.67–304.54] pg/ml, p < 0.001 and IL-10; 15.47 [1.01–270.87] vs. 12.28 [0.96–64.88] and 3.79 [1.24–56.65], p < 0.001 for GC vs. HC). IL-8/IL-10 ratio was lower among GC than HC but higher than FD (3.7 [0.18–38.41] vs. 6.59 [0.98–130.2], p < 0.001 and 4.22 [0.15–61.4], p < 0.01). Circulating levels of IL-8, IL-10 and IL-8/lL-10 ratios were different among H. pylori-infected and non-infected GC than HC (p < 0.001, p < 0.001 and p < 0.01).

Conclusions

Pro-(IL-8)-251 T/A and anti-inflammatory (IL-10)-819 C/T gene polymorphisms and their circulating levels may play a role in H. pylori-associated gastric carcinogenesis in northern India.

Highlights

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  IL-8-251 AA genotype was commoner in GC particularly in the presence of H. pylori and IM.

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  IL-10–819 TT and T carriage were frequent in GC even in the presence of H. pylori.

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  Circulatory IL-8 and IL-10 levels were higher; however, IL-8/IL-10 ratio was lower in GC.

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  IL-8-251A carriage had higher IL-8 but IL-10–1082 A carriage and ATA ⁺ had lower IL-10.