Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia.
OBJECTIVE
To investigate the effects of interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF) gene polymorphisms, Helicobacter pylori (H. pylori) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM).


METHODS
A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progression group (no histological progression from normal or superficial gastritis, n = 137), group I (progressed from normal or superficial gastritis to SCAG, n = 134) and group II (progressed from normal or superficial gastritis to IM, n = 101). IL-8, MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing.


RESULTS
An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection.


CONCLUSIONS
IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.
Li
Zhong-Wu
ZW
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China.
Wu
Ying
Y
Sun
Yu
Y
Liu
Lu-Ying
LY
Tian
Meng-Meng
MM
Feng
Guo-Shuang
GS
You
Wei-Cheng
WC
Li
Ji-You
JY
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005757:Gastritis, Atrophic / Q000209:etiology*; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D007422:Intestines / Q000473:pathology*; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics; D008297:Male; D008679:Metaplasia / Q000209:etiology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000209:etiology; D055815:Young Adult
C508606:CXCL8 protein, human; D016207:Cytokines; D016209:Interleukin-8; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human