Interleukin-8 gene polymorphism associated with susceptibility to non-cardia gastric carcinoma with microsatellite instability.
OBJECTIVE
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.
Shirai
Kennosuke
K
Division of Gastroenterology, Department of Therapeutic Medicine, Nagoya University School of Medicine, Nagoya, Japan.
Ohmiya
Naoki
N
Taguchi
Ayumu
A
Mabuchi
Nobuyuki
N
Yatsuya
Hiroshi
H
Itoh
Akihiro
A
Hirooka
Yoshiki
Y
Niwa
Yasumasa
Y
Mori
Naoyoshi
N
Goto
Hidemi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002299:Cardia; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability; D005838:Genotype; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D004273:DNA, Neoplasm; D016209:Interleukin-8