Tumor Biology

, Volume 37, Issue 2, pp 2233–2242 | Cite as

Association of genetic polymorphisms of interleukins with gastric cancer and precancerous gastric lesions in a high-risk Chinese population

  • Yu-Mei Wang
  • Zhe-Xuan Li
  • Fu-Bing Tang
  • Yang Zhang
  • Tong Zhou
  • Lian Zhang
  • Jun-Ling Ma
  • Wei-Cheng You
  • Kai-Feng Pan
Original Article

Abstract

Helicobacter pylori (H. pylori) infection and cytokine-mediated inflammatory responses play important roles in gastric cancer (GC) pathogenesis. To investigate an association between genetic polymorphisms in interleukin (IL)-, IL-4R, IL-8, IL-10, IL-16, IL-18RAP, IL-22, and IL-32 and risks of GC and its precursors, a population-based study was conducted in Linqu County. Genotypes were determined by Sequenom MassARRAY platform in 132 GC cases and 1198 subjects with gastric lesions. The H. pylori status was determined by 13C-urea breath test (13C-UBT) or enzyme-linked immunosorbent assay (ELISA). Among 11 candidate single nucleotide polymorphisms (SNPs), subjects carrying IL-18RAP rs917997 AA genotype were associated with risk of GC [adjusted odds ratio (OR) = 1.83, 95 % confidence interval (CI) 1.14–2.92] or chronic atrophic gastritis (CAG; OR = 1.55, 95 % CI 1.07–2.24). The risk of GC was also increased in subjects carrying IL-32 rs2015620 A allele (AA + AT; OR = 1.92, 95 % CI 1.09–3.39). Moreover, elevated risks of CAG (OR = 2.64, 95 % CI 1.89–3.69), intestinal metaplasia (IM; OR = 5.58, 95 % CI 3.86–8.05), and dysplasia (DYS; OR = 1.64, 95 % CI 1.18–2.26) were observed in subjects with IL-22 rs1179251 CC genotype. Stratified analysis indicated that risks of GC and its precursors were elevated in subjects with IL-32 rs2015620 A allele (AA + AT) or IL-22 rs1179251 CC genotype and H. pylori infection, and significant interactions between these two SNPs and H. pylori infection were found. These findings suggested that IL-18RAP rs917997, IL-32 rs2015620, IL-22 rs1179251, and interactions between these polymorphisms and H. pylori infection were associated with risks of gastric lesions. Genetic polymorphisms of interleukins may play crucial roles in H. pylori-induced gastric carcinogenesis.

Keywords

Interleukins Genetic polymorphism Gastric cancer Precancerous gastric lesions Helicobacter pylori 

Abbreviations

CAG

Chronic atrophic gastritis

CI

Confidence interval

DYS

Dysplasia

GC

Gastric cancer

H. pylori

Helicobacter pylori

IL

Interleukin

IM

Intestinal metaplasia

OR

Odds ratio

SG

Superficial gastritis

SNP

Single nucleotide polymorphism

Notes

Acknowledgments

This work was supported by grants from National Basic Research Program of China (973 Program: 2010CB529303) and National Natural Science Foundation of China (81171989).

Conflicts of interest

None

Supplementary material

13277_2015_4022_MOESM1_ESM.docx (18 kb)
Table S1 (DOCX 18 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yu-Mei Wang
    • 1
  • Zhe-Xuan Li
    • 1
  • Fu-Bing Tang
    • 1
  • Yang Zhang
    • 1
  • Tong Zhou
    • 1
  • Lian Zhang
    • 1
  • Jun-Ling Ma
    • 1
  • Wei-Cheng You
    • 1
  • Kai-Feng Pan
    • 1
  1. 1.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer EpidemiologyPeking University Cancer Hospital & InstituteBeijingPeople’s Republic of China

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