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 language | English (US) |
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Pages (from-to) | 1129-1135 |
Number of pages | 7 |
Journal | Journal of Gastroenterology and Hepatology (Australia) |
Volume | 21 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2006 |
Keywords
- Cytokine gene polymorphism
- Gastric carcinoma
- Interleukin (IL)-8
- Microsatellite instability
- p53
ASJC Scopus subject areas
- Hepatology
- Gastroenterology