Association Of Interleukin-10 Gene Polymorphism With Cachexia From Patients With Gastric Cancer

Objective Interleukin (IL)-10 is a pleiotropic cytokine that can both stimulate and suppress the inflammatory response. Previous studies have reported that IL-10 production was significantly elevated in cachectic patients, and it has been confirmed that polymorphisms of the IL-10 gene could influence its expression. The present study was to investigate whether IL-10 gene polymorphism have some association with the cachexia from patients with gastric cancer.Methods From October 2008 to May 2009, all of the consecutive patients with gastric cancer admitted to our hospital for surgical treatment were prospectively considered. The patients were divided into 2 groups according to the severity of weight loss during the preceding 6 months and serum C-reactive protein (CRP) level at admission:cachexia group, weight loss>10% plus CRP>10 mg/L; non-cachexia group, weight loss=10%. The serum IL-10 level was examined by radioimmunoassay. Furthermore, we analyzed the polymorphisms at positions-1082A/G,-819T/C and-592A/C in the IL-10 gene promoter, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Linkage and haplotype of IL-10 gene-1082A/G,-819T/C and-592A/C were also studied.Results This study included 223 patients. Of these, cachexia group consisted of 106 patients and non-cachexia group consisted of 117 patients. The serum levels of IL-10 were significantly higher in patients with cachexia than those without (91.64±13.25 ng/mL vs 56.53±12.43 ng/mL, Z=-8.639, P<0.001). An increased frequency of-1082G allele was noted in patients with cachexia (x2=3.868,P=0.049). The frequency of-1082AG and -819CC genotypes were elevated in patients with cachexia than those without (x2=4.412,7.429; P=0.036,0.024). In a logistic regression analysis adjusted for actual weight, carcinoma location and stage, the-1082AG genotype was associated with an odds ratio (OR) of 1.989 (95%CI,1.041-3.802,P=0.037), and the -819CC genotype with an OR of 3.393 (95%CI,1.298-8.871, P=0.013) for cachexia. Furthermore, haplotype analysis revealed that at least five haplotypes (ATA, ACC, GCC, ACA, and ATC) were present in this Chinese population, and the GCC (-1082G/-819C/-592C) haplotype was associated with a significantly increased risk of cachexia as compared with the ATA haplotype (OR=2.21; 95% CI,1.14-4.30; P=0.02).Conclusion Our results suggest that the IL-10 gene GCC haplotype may contribute to the occurrence of cachexia from patients with gastric cancer.