Polymorphisms in the promoter region of macrophage migration inhibitory factor and monocyte chemoattractant protein-1 are associated with increased risk for gastric cancer in a Chinese population
Authors: Shao-Zhang Zhou, Zi-Rong Zeng, Wai-Keung Leung, Joseph J.-S. Sung, Pin-Jin Hu, Mingdong Zhang
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4606 

Gastric cancer is the 2nd leading cause of cancer deaths in the world. Inflammatory cytokine gene polymorphisms are shown to influence the risk of gastric cancer. The cytokine macrophage migration inhibitory factor (MIF) is a constitutive element of the host antimicrobial defenses and promotes proinflammatory function of the innate and acquired immune systems. Monocyte chemoattractant protein-1 (MCP-1) is a beta-chemokine involved in the attraction and accumulation of mononuclear granulocytes toward sites of inflammation. Promoter polymorphisms in MIF (-173 G/C) and MCP-1 (-2518 A/G) affect the level of MIF and MCP-1 expression. These polymorphisms are shown to be associated with increased susceptibility to or severity of chronic inflammatory conditions such as rheumatoid arthritis, ulcerative colitis, or HCV-related liver diseases, but their association with inflammation-associated cancers such as gastric cancer is not studied. To investigate whether these polymorphisms are associated with altered risk for gastric cancer, we carried out a hospital-based case control study. Cases included 206 patients with histologically confirmed non-cardia gastric cancer diagnosed at the teaching hospitals of Sun Yat-Sen University in Guangzhou and Xi’an Medical University in Xi’an. 206 healthy individuals visiting the teaching hospitals for regular physical examinations were recruited as controls. Controls were frequency-matched to cases by gender, age (± 5 years), and the hospital. All study subjects were ethnical Han Chinese. The MIF -173 and MCP-1 -2518 polymorphisms were genotyped by PCR and sequencing of the PCR product. The mean age for cases were 60.2 years (± 11.7) and 58.2 (± 10.7) years for controls. Genotype frequencies of the MIF -173 and MCP-1 -2518 polymorphisms among healthy controls were in Hardy-Weinberg equilibrium. Compared to subjects with a GG genotype at the MIF -173 position, subjects with a GC genotype had an increased risk for gastric cancer after adjusting for age, gender, and H. Pylori infection status (OR: 1.92; 95% CI: 0.99-3.75) and subjects with a homologous CC genotype had a significantly higher risk for gastric cancer (OR: 3.01; 95% CI: 1.52-5.89). Compared to subjects with a CC genotype at the MCP-1 -2518 position, carriers with a G allele were at higher risk for gastric cancer, with an OR of 1.57 (95% CI: 1.01-2.44) for CG genotype and 1.84 (95% CI: 1.05-3.23) for GG genotype. In a combined analysis, subjects homologous for both loci (CC at MIF -173 and GG at MCP-1 -2518) had significantly increased risk for gastric cancer (OR: 8.31; 95% CI: 1.67-41.21). In conclusion, our results suggest that polymorphisms in the promoter region of MIF (G->C at -173) and MCP-1 (C->G at -2518) are associated with increased risk for gastric cancer in the Chinese population.