Interleukin -8 Gene Polymorphism And Gastric Cancer Cachexia, A Qualitative Relationship

Objective:Cytokine interleukin(IL)-8 has been implicated in the development of cancer cachexia.The polymorphism of IL-8 gene,which may affect the production level of cytokine,may be associated with cancer cachexia.The present study was therefore address whether IL-8 gene polymorphism have some association with the cachexia from patients with gastric cancer.Methods:208 consecutive patients with gastric cancer admitted to our hospital for surgical and 190 healthy controls were considered.All patients were divided in to two groups,cachectic patients and non-cachectic patients.Patients were considered cachectic if they had lost＞10%of their preillness stable weight within 6 months.The serum IL-8 level was examined by radioimmunoassay.Furthermore,we identify the polymorphisms at positions -251A/T and +781C/T of the IL-8 gene,using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Linkage and haplotype of IL-8 -251A/T and +781C/T were also studied.Results:The serum levels of IL-8 were significantly elevated in patients with gastric cancer compared with controls(1.115±0.042 ng/ml vs 0.338±0.024 ng/ml,P＜0.001),and were further up-regulated in patients with cachexia than those without(1.389±0.074 ng/ml vs 0.881±0.034 ng/ml,P＜0.001).A predominant frequency of +781 T allele was noted in patients with cachexia(OR=1.765,95%CI:1.192-2.615,P=0.004).The +781 TT genotypes were observed to be associated with a significantly increased risk of cachexia(OR=2.156,95%CI:1.056-4.400,P=0.033),and the difference was enhanced beyond the level of statistical significance when logistic regression was applied (OR=3.500,95%CI:1.406-8.710,P=0.007).Haplotype analysis revealed that A²⁵¹T⁷⁸¹ haplotype(defined by SNPs at positions -251 and +781) was associated with a significantly increased risk of cachexia as compared with the T²⁵¹C⁷⁸¹hplotype(OR=1.69, 95%CI:1.08-2.62,P=0.022).Conclusions:These results suggest that the genetic polymorphisms of proinflammatory cytokine IL-8 may participate in the cause or contribute to cachexia from patients with gastric cancer.