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

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Tumor Biology

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)-1β, 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.

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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

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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).

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Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing, 100142, People’s Republic of China

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

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  1. Yu-Mei Wang
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  2. Zhe-Xuan Li
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Correspondence to Wei-Cheng You or Kai-Feng Pan.

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Wang, YM., Li, ZX., Tang, FB. et al. Association of genetic polymorphisms of interleukins with gastric cancer and precancerous gastric lesions in a high-risk Chinese population. Tumor Biol. 37, 2233–2242 (2016). https://doi.org/10.1007/s13277-015-4022-x

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