Innate immunity and non-Hodgkin's lymphoma (NHL) related genes in a nested case-control study for gastric cancer risk

PLoS One. 2012;7(9):e45274. doi: 10.1371/journal.pone.0045274. Epub 2012 Sep 21.


Objective: 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.

Methods: 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 (DEFA6, DEFB1, JAK3, and ACAA1) and 11 SNPs in nine NHL-related genes (INSL3, CHMP7, BCL2L11, TNFRSF8, RAD50, CASP7, CHUK, CD79B, and CLDN9) with a permutated p-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 H. pylori and CagA sero-positivity. Summarized ORs in the total study population (428 cases and 390 controls) are presented using pooled- and meta-analyses.

Results: Four SNPS had no heterogeneity across the phases: in the meta-analysis, DEFA6 rs13275170 and DEFB1 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). INSL3 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).

Conclusions: 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Asian People / genetics
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Immunity, Innate / genetics*
  • Insulin / genetics*
  • Insulin / immunology
  • Lymphoma, Non-Hodgkin / complications
  • Lymphoma, Non-Hodgkin / genetics*
  • Lymphoma, Non-Hodgkin / immunology
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics*
  • Proteins / immunology
  • Risk
  • Smoking
  • Stomach Neoplasms / complications
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / immunology
  • alpha-Defensins / genetics*
  • alpha-Defensins / immunology
  • beta-Defensins / genetics*
  • beta-Defensins / immunology


  • DEFA6 protein, human
  • DEFB1 protein, human
  • Insulin
  • Leydig insulin-like protein
  • Proteins
  • alpha-Defensins
  • beta-Defensins

Grants and funding

This work was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology [2009-0066258] and by BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology [2011-0001564]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.