Effect of polymorphisms of IL‐1β and TNF‐α genes on CpG island hyper methylation (CIHM) in the nonneoplastic gastric mucosa

Abstract

CpG island hyper methylation (CIHM) is one of the major events in gastric carcinogenesis. To evaluate the influence of host genetic factors in CIHM related carcinogenesis, we investigated the association between common polymorphisms in IL-1β and TNF-α genes, with CIHM status in the nonneoplastic gastric mucosa. Polymorphisms in the IL-1β gene (-31T>C and -511C>T) and the TNF-α gene (-857C>T) were genotyped in 385 cancer-free subjects. CIHM of four candidate genes: p16 (INK4a), p14 (ARF), E-cadherin (CDH1), and death-associated protein kinase (DAP-kinase), were determined by methylation-specific-polymerase chain reaction (MSP). CIHM high was defined as two or more CpG islands methylated. CIHM of all four genes and CIHM high were significantly associated with Helicobacter pylori infection status. In over all, significant marginal association was found between IL-1β-511 TT genotype and reduced susceptibility to CIHM of DAP-kinase (adjusted OR = 0.48, 95% CI = 0.29-0.78) and CIHM high (adjusted OR = 0.53, 95% CI = 0.32-0.86). This association was more enhanced in subjects 65 yr or younger age. We also found positive association between TNF-α-857T carrier and increased susceptibility to CIHM of CDH (adjusted OR = 1.78, 95% CI = 1.01-3.16), and CIHM high (adjusted OR = 1.86, 95% CI = 1.04-3.33) in the same generation. The mean number of CIHM was lower in subjects with IL-1β-511TT genotype, while the mean number was higher in subjects with TNF-α-857 T carrier especially in subjects 65 yr and younger patients. IL-1β-511 TT genotype is associated with reduced susceptibility to CIHM especially in younger generation. Furthermore, the TNF-α-857T carrier is associated with increased susceptibility of CIHM in the same generation.

Association of Cytokine Gene Polymorphisms with Prostate Cancer Risk from a Study in Central China

“…IL-1 β is a 17-kDa cytokine member of the interleukin-1 family, which is involved in inflammation and immunity. The IL-1 β gene is located on chromosome 2q14, and its expression has been reported to be related to different diseases [ 42 , 43 ]. IL- 1 β gene polymorphisms are associated with increased secretion of cytokine IL-1 β when compared to the wild-type gene [ 40 ].…”

“…e IL-1β gene is located on chromosome 2q14, and its expression has been reported to be related to different diseases [42,43]. IL-1β gene polymorphisms are associated with increased secretion of cytokine IL-1β when compared to the wild-type gene [40].…”

The course of gastric cancer following surgery is associated with genetic variations of the interleukin-1 receptor antagonist and interleukin-1β

“…One important step leading to the development of the diffuse type of gastric cancer is hypermethylation of the E-cadherin promoter [23]. There is one report linking the IL-1b C-511T variation with hypermethylation of E-cadherin [24]; however, it seems necessary to further evaluate inflammatory pathways in these distinct histopathological subtypes as this could help us understand the etiology and pathogenesis of these subtypes of gastric cancer.…”

Prostate Stem Cell Antigen Gene Polymorphism Is Associated with H. pylori–related Promoter DNA Methylation in Nonneoplastic Gastric Epithelium

“…The study population comprised of 410 cancer-free subjects, attending the Endoscopy Center of Fujita Health University Hospital (Toyoake, Japan) from January 2005 to January 2010. This cohort was partly recruited from previous study investigating the association between promoter DNA methylation and severity of chronic gastritis (11), NSAIDs use (12), and host genetic factors (13,14), but was independent from our recent studies investigating the DNA methylation in the gastric mucosa after successful H. pylori eradication (15,16). All participants underwent upper gastroscopy as part of a health check, as a secondary procedure following barium X-ray examination for suspected stomach cancer, or for the investigation of abdominal discomfort.…”