白细胞介素-8基因多态性与胃癌恶病质的关系
摘要
目的:研究表明细胞因子白细胞介素(IL)-8与癌性恶病质的发生或发展具有相关性。同时,IL-8基因多态性被证实与其产生水平密切相关,从而可能与癌性恶病质也具有一定的关系。本研究旨在探讨IL-8基因多态性与胃癌恶病质易感性的关系。
方法:选取连续入院的胃癌患者208例,正常对照组190例。胃癌患者分为恶病质组与非恶病质组,将近6个月体重下降＞10%者定义为恶病质病人。应用放射免疫学方法检测血清IL-8含量;通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测IL-8基因-251A/T和+781C/T单核苷酸多态性(SNP),分析其基因型、等位基因型的分布,并对两个SNP位点进行连锁和单体型分析。
结果:胃癌患者血清IL-8含量较正常对照组差别具有显著性(1.115±0.042ng/mlvs 0.338±0.024 ng/ml,P＜0.001),胃癌恶病质组IL-8含量较非恶病质组显著升高(1.389±0.074 ng/ml vs 0.881±0.034 ng/ml,P＜0.001)。基因多态性分析显示胃癌恶病质患者IL-8基因+781 T等位基因频率较非恶病质病人显著升高(OR=1.765,95%CI:1.192-2.615,P=0.004)。IL-8基因+781 TT基因型与胃癌患者恶病质的发生密切相关(OR=2.156,95%CI,1.056-4.400,P=0.033),多因素logistic回归分析行校正检验后显示其为胃癌恶病质可能的高风险性因素(OR=3.500,95%CI:1.406-8.710,P=0.007)。单体型分析显示,IL-8基因A~(251)T~(781)单体型(由IL-8基因-251和+781两个SNP位点组成)与T~(251)C~(781)单体型相比,为胃癌病人恶病质可能的高风险性因素(OR=1.69,95%CI:1.08-2.62,P=0.022)。
结论:细胞因子IL-8基因多态性可能与胃癌患者恶病质的发生发展有关。
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 A~(251)T~(781) haplotype(defined by SNPs at positions -251 and +781) was associated with a significantly increased risk of cachexia as compared with the T~(251)C~(781)hplotype(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.
方法:选取连续入院的胃癌患者208例,正常对照组190例。胃癌患者分为恶病质组与非恶病质组,将近6个月体重下降＞10%者定义为恶病质病人。应用放射免疫学方法检测血清IL-8含量;通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测IL-8基因-251A/T和+781C/T单核苷酸多态性(SNP),分析其基因型、等位基因型的分布,并对两个SNP位点进行连锁和单体型分析。
结果:胃癌患者血清IL-8含量较正常对照组差别具有显著性(1.115±0.042ng/mlvs 0.338±0.024 ng/ml,P＜0.001),胃癌恶病质组IL-8含量较非恶病质组显著升高(1.389±0.074 ng/ml vs 0.881±0.034 ng/ml,P＜0.001)。基因多态性分析显示胃癌恶病质患者IL-8基因+781 T等位基因频率较非恶病质病人显著升高(OR=1.765,95%CI:1.192-2.615,P=0.004)。IL-8基因+781 TT基因型与胃癌患者恶病质的发生密切相关(OR=2.156,95%CI,1.056-4.400,P=0.033),多因素logistic回归分析行校正检验后显示其为胃癌恶病质可能的高风险性因素(OR=3.500,95%CI:1.406-8.710,P=0.007)。单体型分析显示,IL-8基因A~(251)T~(781)单体型(由IL-8基因-251和+781两个SNP位点组成)与T~(251)C~(781)单体型相比,为胃癌病人恶病质可能的高风险性因素(OR=1.69,95%CI:1.08-2.62,P=0.022)。
结论:细胞因子IL-8基因多态性可能与胃癌患者恶病质的发生发展有关。
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 A~(251)T~(781) haplotype(defined by SNPs at positions -251 and +781) was associated with a significantly increased risk of cachexia as compared with the T~(251)C~(781)hplotype(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.
引文
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