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

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 (13)C-urea breath test ((13)C-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.

• Authors: Yu-Mei Wang, Zhe-Xuan Li, Fu-Bing Tang, Yang Zhang, Tong Zhou, Lian Zhang, Jun-Ling Ma, Wei-Cheng You, Kai-Feng Pan
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 2 Pg. 2233-42 (Feb 2016) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26358252 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• IL18RAP protein, human
• IL32 protein, human
• Interleukin-18 Receptor beta Subunit
• Interleukins

Topics

• Adult
• Asian People (genetics)
• Enzyme-Linked Immunosorbent Assay
• Female
• Genetic Predisposition to Disease (genetics)
• Genotype
• Helicobacter Infections (complications, genetics)
• Humans
• Interleukin-18 Receptor beta Subunit (genetics)
• Interleukins (genetics)
• Male
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Polymorphism, Single Nucleotide
• Precancerous Conditions (genetics, microbiology)
• Stomach Neoplasms (genetics, microbiology)
• Interleukin-22