Cancer risk to the gastric corpus in Japanese, its correlation withinterleukin‐1βgene polymorphism (+3953*T) and Epstein‐Barr virus infection

Abstract

Polymorphisms of interleukin-1 (IL-1) genes have been reported to modify the risk of gastric carcinoma (GC) in Caucasians. The significance of IL-1b gene polymorphisms was evaluated in Japanese GC patients with or without infection of Helicobacter pylori and Epstein Barr virus (EBV) with special reference to the topographic features of GC. IL-1b gene polymorphisms at positions -511 and +3953 were evaluated by PCR-RFLP and a penta-allelic polymorphism of IL-1RA by PCR in healthy controls (n = 103) and GC (n =140; corpus 95, antrum 45). EBV-infection was determined in the neoplastic tissues by EBER1 in situ hybridization, and H. pylori infection in nonneoplastic gastric mucosa by PCR targeting of the H. pylori urease A gene. GC consisted of EBV-associated (n = 24) and EBV-negative (n = 116) patients, whereas H. pylori infection was positive in 130 cases. Among IL-1b gene polymorphisms, genotype IL-1b+3953 C/T was more frequent in the EBV-negative (21%) and corpus GC (23%) patients, compared to the controls (10%), respectively, although there was no genotype IL-1b+3953 T/T in either group. Thus, the effect of IL-1b+3953 T was statistically significant in logistic regression models adjusted for age in EBV negativity (odds ratio [OR] 2.27, 95% confidence interval [CI] 1.02-5.05) and in the corpus GC (2.70, 1.19-6.12) with highest OR 3.55 (1.54-8.23) in EBV-negative corpus GC. There was no significant influence of IL-1 gene polymorphism in EBV-associated GC, but it occurred predominantly in the corpus (24/24) compared to EBV-negative GC (71/116) (p = 0.00002). There was no correlation between H. pylori infection and IL-1 gene polymorphism in GC. The cancer risk of the gastric corpus in Japanese is influenced by IL-1b+3953 polymorphisms. On the other hand, the risk of EBV-associated GC, which occurs predominantly in the corpus, is not influenced by this pro-inflammatory polymorphism. ' 2005 Wiley-Liss, Inc.

IL-1.BETA. Genotype-Related Effect of Prednisolone on IL-1.BETA. Production in Human Peripheral Blood Mononuclear Cells under Acute Inflammation

“…The IL-1b GϪ1470C polymorphism in the promoter region of IL-1b was recently newly identified in the Chinese population at a frequency of 41.67%, 13) and here, for the first time we confirmed the presence of this polymorphism in healthy Japanese at a frequency of 30.0% (Table 1). Three other IL-1b polymorphisms CϪ511T, TϪ31C and C3954T, have been identified in the Japanese population [18][19][20] and their allelic and genotype frequencies were close to those obtained in the present study. Table 2 shows the estimated frequencies of the IL-1b haplotypes in the healthy Japanese subjects.…”

Interleukin-1β and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Gastric Cancer: A Meta-analysis

“…It can also alter the assumed type I error rate (51,52 The studies differed in the extent of characterization of the tumors. Twenty-one reports mentioned histologic confirmation of gastric cancer cases, but the remaining four used the diagnosis from medical records (or tumor registries) or did not clarify the source of diagnosis (17,26,30,31). Regarding tumor location, 12 studies included cases from more than one gastric site (three of them presented stratified analyses), eight included only noncardia cases, and six did not report the location.…”

“…D, Caucasians, noncardia gastric cancer cases (P heterogeneity = 0.708). IL1B+3954 in Asians and Hispanics (14,15,31), a dominant genetic model was assumed. Figure 3 presents the random-effects OR for gastric cancer risk for IL1B+3954T carriers compared with the C/C genotype.…”

MicroRNA dysregulation in gastric cancer: a new player enters the game

“…Interactions among host, environmental and bacterial factors also influence the disease outcome. For instance, strong inflammatory response as a result of cytokine gene polymorphisms (Zambon et al, 2004;Lee et al, 2005;Sakuma et al, 2005), infection with the CagA-positive strain of H. pylori (Blaser et al, 1995) and diet high in salt and nitrate are synergistic risk factors for gastric cancer (Yamaguchi and Kakizoe, 2001). Clinically, the absence of specific symptoms renders early diagnosis of this deadly disease difficult.…”