Interleukin-8 gene polymorphism associated with susceptibility to non-cardia gastric carcinoma with microsatellite instability

Kennosuke Shirai, Naoki Ohmiya, Ayumu Taguchi, Nobuyuki Mabuchi, Hiroshi Yatsuya, Akihiro Itoh, Yoshiki Hirooka, Yasumasa Niwa, Naoyoshi Mori, Hidemi Goto

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background and Aim: Gastric carcinoma (GC) with microsatellite instability (MSI) exhibits clinicopathological characteristics distinct from microsatellite-stable (MSS) GC. Both MSI and MSS carcinomas are mostly associated with chronic gastritis infected by Helicobacter pylori (Hp). The relationship between Hp-induced inflammation and the mutator pathway of MSI remains unclear. Recently, cytokine polymorphisms have been reported to affect the development of non-cardia GC. The objective of this study was to elucidate the relationship between cytokine polymorphisms and MSI phenotypes. Methods: In a case-control study including 482 controls and 181 patients with GC, interleukin (IL)-8 -251, IL-1B -511, IL-1RN, and tumor necrosis factor-A (TNFA) -857 polymorphisms were genotyped. The presence of MSI and mutations in exons 5 to 8 of the p53 gene were examined in GC cases. All clinicopathological data were collected from individual records. Results: High and low frequency of MSI (MSI-H and MSI-L) and MSS were detected in 16 (8.8%), 14 (7.7%) and 151 (83.4%) GC cases, respectively. We found that IL-8 -251 T/T genotype was significantly associated with increased risk of MSI-H GC compared to MSI-L/MSS GC and controls. We found no association between other cytokine polymorphisms and MSI-H GC. The percentage of smokers and the frequency of p53 mutations were significantly lower in MSI-H than MSI-L/MSS GC. We found significant associations of MSI-H with synchronous or metachronous multiple occurrence, antral location and intestinal type. Conclusions: Our study shows that MSI-H GC is associated with IL-8-251 T/T (low expression genotype) and is inversely correlated with cigarette smoking.

Original languageEnglish
Pages (from-to)1129-1135
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume21
Issue number7
DOIs
Publication statusPublished - 07-2006

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Microsatellite Instability
Interleukin-8
Stomach
Carcinoma
Genes
Microsatellite Repeats
Interleukins
Cytokines
Helicobacter pylori
Genotype
p53 Genes
Gastritis
Mutation Rate

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Shirai, Kennosuke ; Ohmiya, Naoki ; Taguchi, Ayumu ; Mabuchi, Nobuyuki ; Yatsuya, Hiroshi ; Itoh, Akihiro ; Hirooka, Yoshiki ; Niwa, Yasumasa ; Mori, Naoyoshi ; Goto, Hidemi. / Interleukin-8 gene polymorphism associated with susceptibility to non-cardia gastric carcinoma with microsatellite instability. In: Journal of Gastroenterology and Hepatology (Australia). 2006 ; Vol. 21, No. 7. pp. 1129-1135.
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abstract = "Background and Aim: Gastric carcinoma (GC) with microsatellite instability (MSI) exhibits clinicopathological characteristics distinct from microsatellite-stable (MSS) GC. Both MSI and MSS carcinomas are mostly associated with chronic gastritis infected by Helicobacter pylori (Hp). The relationship between Hp-induced inflammation and the mutator pathway of MSI remains unclear. Recently, cytokine polymorphisms have been reported to affect the development of non-cardia GC. The objective of this study was to elucidate the relationship between cytokine polymorphisms and MSI phenotypes. Methods: In a case-control study including 482 controls and 181 patients with GC, interleukin (IL)-8 -251, IL-1B -511, IL-1RN, and tumor necrosis factor-A (TNFA) -857 polymorphisms were genotyped. The presence of MSI and mutations in exons 5 to 8 of the p53 gene were examined in GC cases. All clinicopathological data were collected from individual records. Results: High and low frequency of MSI (MSI-H and MSI-L) and MSS were detected in 16 (8.8{\%}), 14 (7.7{\%}) and 151 (83.4{\%}) GC cases, respectively. We found that IL-8 -251 T/T genotype was significantly associated with increased risk of MSI-H GC compared to MSI-L/MSS GC and controls. We found no association between other cytokine polymorphisms and MSI-H GC. The percentage of smokers and the frequency of p53 mutations were significantly lower in MSI-H than MSI-L/MSS GC. We found significant associations of MSI-H with synchronous or metachronous multiple occurrence, antral location and intestinal type. Conclusions: Our study shows that MSI-H GC is associated with IL-8-251 T/T (low expression genotype) and is inversely correlated with cigarette smoking.",
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Interleukin-8 gene polymorphism associated with susceptibility to non-cardia gastric carcinoma with microsatellite instability. / Shirai, Kennosuke; Ohmiya, Naoki; Taguchi, Ayumu; Mabuchi, Nobuyuki; Yatsuya, Hiroshi; Itoh, Akihiro; Hirooka, Yoshiki; Niwa, Yasumasa; Mori, Naoyoshi; Goto, Hidemi.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 21, No. 7, 07.2006, p. 1129-1135.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interleukin-8 gene polymorphism associated with susceptibility to non-cardia gastric carcinoma with microsatellite instability

AU - Shirai, Kennosuke

AU - Ohmiya, Naoki

AU - Taguchi, Ayumu

AU - Mabuchi, Nobuyuki

AU - Yatsuya, Hiroshi

AU - Itoh, Akihiro

AU - Hirooka, Yoshiki

AU - Niwa, Yasumasa

AU - Mori, Naoyoshi

AU - Goto, Hidemi

PY - 2006/7

Y1 - 2006/7

N2 - Background and Aim: Gastric carcinoma (GC) with microsatellite instability (MSI) exhibits clinicopathological characteristics distinct from microsatellite-stable (MSS) GC. Both MSI and MSS carcinomas are mostly associated with chronic gastritis infected by Helicobacter pylori (Hp). The relationship between Hp-induced inflammation and the mutator pathway of MSI remains unclear. Recently, cytokine polymorphisms have been reported to affect the development of non-cardia GC. The objective of this study was to elucidate the relationship between cytokine polymorphisms and MSI phenotypes. Methods: In a case-control study including 482 controls and 181 patients with GC, interleukin (IL)-8 -251, IL-1B -511, IL-1RN, and tumor necrosis factor-A (TNFA) -857 polymorphisms were genotyped. The presence of MSI and mutations in exons 5 to 8 of the p53 gene were examined in GC cases. All clinicopathological data were collected from individual records. Results: High and low frequency of MSI (MSI-H and MSI-L) and MSS were detected in 16 (8.8%), 14 (7.7%) and 151 (83.4%) GC cases, respectively. We found that IL-8 -251 T/T genotype was significantly associated with increased risk of MSI-H GC compared to MSI-L/MSS GC and controls. We found no association between other cytokine polymorphisms and MSI-H GC. The percentage of smokers and the frequency of p53 mutations were significantly lower in MSI-H than MSI-L/MSS GC. We found significant associations of MSI-H with synchronous or metachronous multiple occurrence, antral location and intestinal type. Conclusions: Our study shows that MSI-H GC is associated with IL-8-251 T/T (low expression genotype) and is inversely correlated with cigarette smoking.

AB - Background and Aim: Gastric carcinoma (GC) with microsatellite instability (MSI) exhibits clinicopathological characteristics distinct from microsatellite-stable (MSS) GC. Both MSI and MSS carcinomas are mostly associated with chronic gastritis infected by Helicobacter pylori (Hp). The relationship between Hp-induced inflammation and the mutator pathway of MSI remains unclear. Recently, cytokine polymorphisms have been reported to affect the development of non-cardia GC. The objective of this study was to elucidate the relationship between cytokine polymorphisms and MSI phenotypes. Methods: In a case-control study including 482 controls and 181 patients with GC, interleukin (IL)-8 -251, IL-1B -511, IL-1RN, and tumor necrosis factor-A (TNFA) -857 polymorphisms were genotyped. The presence of MSI and mutations in exons 5 to 8 of the p53 gene were examined in GC cases. All clinicopathological data were collected from individual records. Results: High and low frequency of MSI (MSI-H and MSI-L) and MSS were detected in 16 (8.8%), 14 (7.7%) and 151 (83.4%) GC cases, respectively. We found that IL-8 -251 T/T genotype was significantly associated with increased risk of MSI-H GC compared to MSI-L/MSS GC and controls. We found no association between other cytokine polymorphisms and MSI-H GC. The percentage of smokers and the frequency of p53 mutations were significantly lower in MSI-H than MSI-L/MSS GC. We found significant associations of MSI-H with synchronous or metachronous multiple occurrence, antral location and intestinal type. Conclusions: Our study shows that MSI-H GC is associated with IL-8-251 T/T (low expression genotype) and is inversely correlated with cigarette smoking.

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