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环氧化酶-2 活性和 C 反应蛋白水平在非黑素瘤皮肤癌患者中的作用。-765G>C PTGS2 多态性与 NMSC 风险。

Role of COX-2 activity and CRP levels in patients with non-melanoma skin cancer. -765G>C PTGS2 polymorphism and NMSC risk.

机构信息

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

出版信息

Arch Dermatol Res. 2012 Jul;304(5):335-42. doi: 10.1007/s00403-011-1194-0. Epub 2011 Dec 8.

DOI:10.1007/s00403-011-1194-0
PMID:22159575
Abstract

Non-melanoma skin cancer is one of the most common of all cancers and the incidence has increased in the last years as a result of many factors including increased tanning, life style and possible global climate change. Inflammation plays an important role in cancer development and is frequently evaluated by serum C-reactive protein (CRP) levels. PTGS2 -765C allele coding for COX-2 has been found to be associated with lower plasma levels of CRP. The objectives of this study are: evaluation of the association between PTGS2 -765G>C polymorphism and the occurrence of non-melanoma skin cancer, the relationship between this polymorphism and cyclooxygenase-2 activity in skin tissue, as well as the correlation with serum CRP levels in patients with non-melanoma skin cancer. We used PCR-RFLP technique to explore -765G>C PTGS2 gene polymorphism, colorimetric analysis for cyclooxygenase-2 activity in skin tissue and immunoturbidimetric assay for CRP serum levels in 174 patients with non-melanoma skin cancer [54 patients with basal cell carcinoma (BCC) and 120 patients with squamous cell carcinoma (SCC)] and 80 healthy subjects. PTGS2 -765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. We observed a significant increase in COX-2 activity in SCC and BCC patients compared to control tissue (0.58 ± 0.11 and 0.63 ± 0.09 U/mg protein, respectively vs. 0.16 ± 0.01 U/mg protein). BCC and SCC intra-group analysis showed lower COX-2 activity in C-allele carriers versus non-carriers (p < 0.001 and p < 0.0001, respectively). In BCC and SCC patients with GG genotype, CRP level is significantly increased compared to control group (p < 0.0001 and p < 0.0001, respectively). Intra-group comparison of CRP levels showed significantly lower CRP levels in patients carrying C-allele compared to GG homozygotes in BCC (p = 0.0001) and SCC patients (p < 0.0001). PTGS2 -765G>C polymorphism failed to show an association with non-melanoma skin cancer risk. Regarding prognostic indicators, no consistent association emerged between PTGS2 -765G>C polymorphism and COX-2 activity or CRP levels.

摘要

非黑色素瘤皮肤癌是最常见的癌症之一,近年来由于许多因素的影响,包括日光浴、生活方式和可能的全球气候变化,其发病率有所增加。炎症在癌症发展中起着重要作用,常通过血清 C 反应蛋白(CRP)水平来评估。已经发现 PTGS2-765C 等位基因编码的 COX-2 与 CRP 血浆水平较低有关。本研究的目的是:评估 PTGS2-765G>C 多态性与非黑色素瘤皮肤癌发生的相关性,该多态性与皮肤组织中环氧化酶-2 活性的关系,以及与非黑色素瘤皮肤癌患者血清 CRP 水平的相关性。我们使用 PCR-RFLP 技术探讨 PTGS2-765G>C 基因多态性,比色分析法检测皮肤组织中环氧化酶-2 活性,免疫比浊法检测血清 CRP 水平,共纳入 174 例非黑色素瘤皮肤癌患者[54 例基底细胞癌(BCC)和 120 例鳞状细胞癌(SCC)]和 80 例健康对照。PTGS2-765G>C 多态性与非黑色素瘤皮肤癌风险无相关性。与对照组织相比,我们观察到 SCC 和 BCC 患者 COX-2 活性显著增加(分别为 0.58±0.11 和 0.63±0.09 U/mg 蛋白,0.16±0.01 U/mg 蛋白)。BCC 和 SCC 组内分析显示 C 等位基因携带者 COX-2 活性低于非携带者(p<0.001 和 p<0.0001)。在 GG 基因型的 BCC 和 SCC 患者中,CRP 水平与对照组相比显著升高(p<0.0001 和 p<0.0001)。组内 CRP 水平比较显示,BCC 和 SCC 患者中 C 等位基因携带者的 CRP 水平明显低于 GG 纯合子(p=0.0001 和 p<0.0001)。PTGS2-765G>C 多态性与非黑色素瘤皮肤癌风险无相关性。关于预后指标,PTGS2-765G>C 多态性与 COX-2 活性或 CRP 水平之间没有一致的相关性。

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