Circulating Inflammation-related Markers and Advanced Gastric Premalignant Lesions.

BACKGROUND AND AIM: Chronic Helicobacter pylori infection causes gastric mucosal inflammation as an important antecedent of gastric cancer. We aimed to evaluate associations of blood markers of inflammation with gastric intestinal metaplasia and dysplasia in H. pylori-infected individuals.

METHODS: We compared pre-treatment serum levels of immune- and inflammation-related markers between 99 individuals with intestinal metaplasia or dysplasia, and 75 control individuals with non-atrophic gastritis within an H. pylori eradication trial in Mexico. Serum levels of 28 markers measured with Luminex bead-based assays were categorized in tertiles as low (T1), middle (T2) and high (T3). Logistic regression models were used to calculate age- and sex- adjusted odds ratios (OR) and 95% confidence intervals (CI). All statistical tests were two-sided and significance values were adjusted for multiple comparisons using false discovery rate (FDR) methods.

RESULTS: Five markers were nominally associated (p-trends <0.05) with the presence of advanced premalignant gastric lesions. Adjusted ORs (95% CI) of T2 and T3 vs. T1 were 4.09 (1.65-10.17) and 3.08 (1.23-7.68) for CCL3/MIP1a, 3.21 (1.33-7.75) and 2.69 (1.10-6.57) for CCL20/MIP3a levels, 1.79 (0.77-4.18) and 2.39 (1.02-5.60) for IL1β, 1.34 (0.56-3.19) and 3.02 (1.29-7.12) for IL4, and 1.07 (0.44-2.59) and 3.07 (1.32-7.14) for IL5, respectively. Two (IL4 and IL5) of the five markers had FDR adjusted p-trend <0.2.

CONCLUSIONS: Our results suggest certain Th2 and other cytokines may have a role in promoting carcinogenesis in the setting of H. pylori infection. Additional research is needed to replicate these findings, extend to pre-diagnostic samples and elucidate the underlying mechanisms.