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EGF、TGF-β 和 TNF-α 基因的单核苷酸多态性与胰腺癌患者。

Single nucleotide polymorphisms of genes for EGF, TGF-β and TNF-α in patients with pancreatic carcinoma.

机构信息

Department for Vascular and Endovascular Surgery, Johann Wolfgang Goethe University Hospital Frankfurt, Germany.

出版信息

Cancer Genomics Proteomics. 2012 Sep-Oct;9(5):287-95.

PMID:22990108
Abstract

AIM

To show whether single nucleotide polymorphisms (SNPs) of Epidermal growth factor (EGF)-61()A/G, Transforming growth factor beta 1 (TGF-B1) - 509()T/C and Tumor necrosis factor-alpha (TNF-A) -308(*)A/G are associated with the survival rate after pancreatic cancer surgery and with the frequency of post-operative complications.

PATIENTS AND METHODS

EGF 61()A/G, TGF-B1-509()T/C and TNF-A-308(*)A/G genotypes were analyzed in patients who underwent pylorus-preserving pancreaticoduonectomy for pancreatic carcinoma and were determined by means of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The association of each genetic polymorphism with clinical and pathological data of the patients and early tumor recurrence were evaluated.

RESULTS

A significantly lower median survival duration was found in EGF 61()AA homozygotes, as compared to the AG heterozygous group. There was also a significantly lower median survival duration in the TNF-A-308() AA homozygote group as compared to the AG and GG groups. Survival duration in patients had no correlation with TGF-B1 -509()T/C polymorphism. There was a significantly lower median survival duration in the TNF-A -308() AA homozygous group, as compared to the AG and GG group in a Cox proportional hazard model. The frequency of the TGF-B1 T-allele was higher among patients with leakage of the pancreatic anastomosis. The frequency of the TGF-B1 TC genotype was significantly higher among patients who developed leakage of the biliodigestive anastomosis as compared with the TGF-B1 CC genotype. The frequency of TGF-B1 T-carriers (i.e. TT+TC) was significantly higher among patients with leakage of the biliodigestive anastomosis, as compared to these with the TGF-B1 CC genotype. In a Cox proportional hazard model, only wound infection had a significant correlation with long-term survival duration of patients with pancreatic cancer.

CONCLUSION

There appears to be a significant correlation of the EGF-61() AA and of the TNF-A -308() AA polymorphism with lower survival duration in patients with resectable pancreatic carcinoma. The presence of wound infection was associated with poor prognosis. TGF-B1-509(*) T-carrying genotypes were more frequent in paitents with severe post-operative complications.

摘要

目的

研究表皮生长因子(EGF)-61()A/G、转化生长因子-β1(TGF-β1)-509()T/C 和肿瘤坏死因子-α(TNF-α)-308(*)A/G 的单核苷酸多态性(SNPs)是否与胰腺癌手术后的生存率以及术后并发症的发生频率有关。

方法

对接受保留幽门的胰十二指肠切除术的胰腺癌患者进行 EGF 61()A/G、TGF-β1-509()T/C 和 TNF-α-308(*)A/G 基因分型,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法确定。评估每种遗传多态性与患者的临床和病理数据以及早期肿瘤复发的关系。

结果

EGF 61()AA 纯合子患者的中位生存时间明显低于 EGF 61()AG 杂合子患者。TNF-α-308()AA 纯合子患者的中位生存时间也明显低于 TNF-α-308()AG 和 GG 组。患者的生存时间与 TGF-β1-509()T/C 多态性无关。在 Cox 比例风险模型中,TNF-α-308()AA 纯合子患者的中位生存时间明显低于 TNF-α-308(*)AG 和 GG 组。在发生胰吻合口漏的患者中,TGF-β1 T 等位基因的频率较高。与 TGF-β1 CC 基因型相比,TGF-β1 TC 基因型在发生胆肠吻合口漏的患者中更为常见。与 TGF-β1 CC 基因型相比,TGF-β1 T 携带者(即 TT+TC)在发生胆肠吻合口漏的患者中更为常见。在 Cox 比例风险模型中,只有伤口感染与胰腺癌患者的长期生存时间有显著相关性。

结论

在可切除胰腺癌患者中,EGF-61()AA 和 TNF-α-308()AA 多态性与生存率降低有显著相关性。伤口感染的存在与预后不良有关。TGF-β1-509(*)T 携带基因型在发生严重术后并发症的患者中更为常见。

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