Influence of IL1B polymorphism on CpG island hypermethylation in Helicobacter pylori-infected gastric cancer

• Published in: Virchows Archiv : an international journal of pathology Vol. 456; no. 6; pp. 647 - 652
• Main Authors: Yoo, Eun Joo, Park, Seog-Yun, Cho, Nam-Yun, Kim, Nayoung, Lee, Hye Seung, Kim, Donguk, Kang, Gyeong Hoon
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.06.2010; Springer; Springer Nature B.V
• Subjects: Bacterial diseases; Bacterial diseases of the digestive system and abdomen; Biological and medical sciences; CpG Islands; DNA Methylation; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Helicobacter Infections - complications; Helicobacter pylori; Human bacterial diseases; Humans; Infectious diseases; Interleukin-1beta - genetics; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Original Article; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymorphism, Single Nucleotide; Stomach Neoplasms - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; DNA methylation; IL1B; Single nucleotide polymorphism; Genetic variability; Spirillales; Nucleotide sequence; Spirillaceae; Genotype; Malignant tumor; Stomach cancer; Infection; Anatomic pathology; Helicobacter pylori; GC rich sequence; DNA; Bacteriosis; Bacteria; Digestive diseases; Methylation; Cancer; Gastric disease
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-010-0918-4

Helicobacter pylori infection can induce aberrant CpG island hypermethylation in gastric mucosal epithelial cells. Single nucleotide polymorphisms of proinflammatory cytokine genes encoding for interleukin 1B ( IL1B ), IL6 , and IL8 have been demonstrated to be associated with an increased risk of gastric cancer. To identify the influence of host genetic factors in CpG island hypermethylation induced by H. pylori infection, we analyzed H. pylori- infected chronic gastritis ( n  = 111) and gastric cancer samples ( n  = 78) for the methylation status of eight genes previously shown to be hypermethylated in chronic gastritis and single nucleotide polymorphisms of IL1B , IL6 , and IL8 . The methylation levels were then compared between different genotypes. Gastric cancers from patients with the IL1B -511T/T allele showed significantly higher methylation levels in five genes as compared with gastric cancers from IL1B -511 C carriers ( P  < 0.05). An increased level of hypermethylation in association with the IL1B -511T/T allele was observed in chronic gastritis samples, but the association was not statistically significant. These findings suggest that the IL1B -511T/T allele is associated with enhanced hypermethylation of multiple CpG island loci, which might contribute to an increase in the risk for gastric cancer in individuals with H. pylori infection and IL1B -511T/T allele.