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白细胞介素-6基因多态性对非小细胞肺癌预后影响的研究

A study on the effect of IL-6 gene polymorphism on the prognosis of non-small-cell lung cancer.

作者信息

Jia Wei, Fei Guang-He, Hu Jie-Gui, Hu Xian-Wei

机构信息

Pulmonary Department, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.

出版信息

Onco Targets Ther. 2015 Sep 23;8:2699-704. doi: 10.2147/OTT.S84636. eCollection 2015.

Abstract

BACKGROUND

Lung cancer is one of the most commonly diagnosed clinical diseases. IL-6 is a multifunctional cytokine that is related to chemotactic factors and tumor biological regulation. -174G/C polymorphism in the promoter region of the IL-6 gene single-nucleotide polymorphism is the -174 position change from G to C. However, the relationship between the IL-6 gene polymorphism and prognosis of lung cancer is elusive. Therefore, the aim of this study was to evaluate the effect of -174G/C polymorphism on the prognosis of patients with non-small-cell lung cancer (NSCLC).

METHODS

DNA was extracted from the peripheral blood of 434 cases diagnosed with NSCLC by cytologic or histologic examination. Polymerase chain reaction-restriction fragment length polymorphism (NlaIII) was used to detect the genotype of -174G/C. Based on the functional activity of the IL-6 gene polymorphism, genotypes were divided into G vector (CG/GG) (high yield) and CC genotype (low yield). Prognosis of patients was analyzed and independent risk factors evaluated. A quantitative analysis of the degree of pain after diagnosis was performed to evaluate the correlations between gene polymorphisms and the degree of pain and use of analgesics.

RESULTS

Survival analysis showed that survival of the patients carrying the G allele (CG/GG) was significantly lower than that of patients with CC genotype (42.31 versus 62.79 months; P=0.032). The IL-6 gene promoter region revealed the presence of polymorphic variants, which may be associated with changes in the gene transcription process that affect the level of serum cytokines. IL-6 -174G/C gene polymorphism is associated with a significant morphine equivalent daily dose (IL-6 GG, 69.61; GC, 73.17; CC, 181.67; P=0.004). Homozygous IL-6 -174C/C genotype carriers required higher doses of opioids than GG or GC carriers.

CONCLUSION

Polymorphism of -174G/C in IL-6 is closely related to cancer pain in NSCLC patients, the use of analgesics, and survival prognosis. It is necessary to further confirm the related results and determine the underlying pathogenic mechanisms.

摘要

背景

肺癌是最常见的临床诊断疾病之一。白细胞介素-6(IL-6)是一种多功能细胞因子,与趋化因子和肿瘤生物学调节有关。IL-6基因单核苷酸多态性启动子区域的-174G/C多态性是指-174位置由G变为C。然而,IL-6基因多态性与肺癌预后之间的关系尚不清楚。因此,本研究的目的是评估-174G/C多态性对非小细胞肺癌(NSCLC)患者预后的影响。

方法

从434例经细胞学或组织学检查确诊为NSCLC的患者外周血中提取DNA。采用聚合酶链反应-限制性片段长度多态性(NlaIII)检测-174G/C的基因型。根据IL-6基因多态性的功能活性,将基因型分为G载体(CG/GG)(高产量)和CC基因型(低产量)。分析患者的预后并评估独立危险因素。对诊断后的疼痛程度进行定量分析,以评估基因多态性与疼痛程度和镇痛药使用之间的相关性。

结果

生存分析显示,携带G等位基因(CG/GG)的患者生存率显著低于CC基因型患者(42.31个月对62.79个月;P=0.032)。IL-6基因启动子区域存在多态性变异,这可能与影响血清细胞因子水平的基因转录过程变化有关。IL-6 -174G/C基因多态性与显著的每日吗啡等效剂量相关(IL-6 GG,69.61;GC,73.17;CC,181.67;P=0.004)。纯合子IL-6 -174C/C基因型携带者比GG或GC携带者需要更高剂量的阿片类药物。

结论

IL-6中-174G/C多态性与NSCLC患者的癌痛、镇痛药使用及生存预后密切相关。有必要进一步证实相关结果并确定潜在的致病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9c/4590668/ba55d195272d/ott-8-2699Fig1.jpg

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