title: 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.affiliation: 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.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhe-Xuan
authors.initials: ZX
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Fu-Bing
authors.initials: FB
authors.lastname: Tang
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Ma
authors.affiliation: 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. weichengyou@yahoo.com.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: You
authors.affiliation: 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. pankaifeng2002@yahoo.com.
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Pan
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics; D006801:Humans; D053728:Interleukin-18 Receptor beta Subunit / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000235:genetics* / Q000382:microbiology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology; D000097043:Interleukin-22
chemical_list: D053728:Interleukin-18 Receptor beta Subunit; D007378:Interleukins; D000097043:Interleukin-22; C115629:IL18RAP protein, human; C496971:IL32 protein, human
keywords: Gastric cancer; Genetic polymorphism; Helicobacter pylori; Interleukins; Precancerous gastric lesions