Innate Immunity and Non-Hodgkin’s Lymphoma (NHL) Related Genes in a Nested Case-Control Study for Gastric Cancer Risk

Abstract

<div><h3>Objective</h3><p>Genetic variants regulating the host immune system may contribute to the susceptibility for the development of gastric cancer. Little is known about the role of the innate immunity- and non-Hodgkin’s lymphoma (NHL)-related genes for gastric cancer risk. This nested case-control study was conducted to identify candidate genes for gastric cancer risk for future studies.</p> <h3>Methods</h3><p>In the Discovery phase, 3,072 SNPs in 203 innate immunity- and 264 NHL-related genes using the Illumine GoldenGateTM OPA Panel were analyzed in 42 matched case-control sets selected from the Korean Multi-center Cancer Cohort (KMCC). Six significant SNPs in four innate immunity (<em>DEFA6, DEFB1, JAK3,</em> and <em>ACAA1</em>) and 11 SNPs in nine NHL-related genes (<em>INSL3, CHMP7, BCL2L11, TNFRSF8, RAD50, CASP7, CHUK, CD79B,</em> and <em>CLDN9</em>) with a permutated <em>p</em>-value <0.01 were re-genotyped in the Replication phase among 386 cases and 348 controls. Odds ratios (ORs) for gastric cancer risk were estimated adjusting for age, smoking status, and <em>H. pylori</em> and CagA sero-positivity. Summarized ORs in the total study population (428 cases and 390 controls) are presented using pooled- and meta-analyses.</p> <h3>Results</h3><p>Four SNPs had no heterogeneity across the phases: in the meta-analysis, <em>DEFA6</em> rs13275170 and <em>DEFB1</em> rs2738169 had both a 1.3-fold increased odds ratio (OR) for gastric cancer (95% CIs = 1.1–1.6; and 1.1–1.5, respectively). <em>INSL3</em> rs10421916 and rs11088680 had both a 0.8-fold decreased OR for gastric cancer (95% CIs = 0.7–0.97; and 0.7–0.9, respectively).</p> <h3>Conclusions</h3><p>Our findings suggest that certain variants in the innate immunity and NHL-related genes affect the gastric cancer risk, perhaps by modulating infection-inflammation-immunity mechanisms that remain to be defined.</p> </div