Mohamadkhani Ashraf, Pourshams Akram, Viti Jessica, Cellai Filippo, Mortazavi Kamran, Sharafkhah Maryam, Sotoudeh Masoud, Malekzadeh Reza, Boffetta Paolo, Peluso Marco
Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Email:
Asian Pac J Cancer Prev. 2017 May 1;18(5):1349-1355. doi: 10.22034/APJCP.2017.18.5.1349.
Background: DNA damage accumulation has been linked to the cancer phenotype. The purpose of this study was to compare the levels of DNA base 8-hydroxy-2′-deoxyguanosine (8-OHdG) and C-reactive protein (CRP) inflammatory markers in healthy controls and pancreatic cancer patients from a hospital-based case-control study. Materials and Methods: Fifty-five pancreatic cancer patients and 55 healthy controls were enrolled from a pool of patients referred to the Endoscopic Ultrasound (EUS) center. Analysis of DNA content of peripheral blood cells was conducted for 8-OHdG with the 32P-postlabelling assay. Serum CRP levels were measured by high-sensitivity assays and demographic data for comparison were collected from individual medical records. Results: The group of cases showed significant increased median (IQR) 8-OHdG DNA adducts/106 nucleotides and CRP compared to the controls (208.8 (138.0-340.8) vs 121.8 (57.7-194.8) RAL value; P<0.001) and (3.5 (1.5-8.6) vs 0.5 (0.2-1.5) mg/L P<0.001). A number of conditional regression models confirmed associations of pancreatic cancer with oxidative DNA damage in peripheral leukocytes.Conclusions: Our findings suggest the importance of leukocyte 8-OHdG adducts as an indicator for systemic oxidative DNA damage in pancreatic cancer patients. In addition to increase in the CRP inflammatory marker, this supports the impact of inflammation in the occurrence of pancreatic cancer as well as inflammatory responses during cancer development.
DNA损伤积累与癌症表型相关。本研究旨在通过一项基于医院的病例对照研究,比较健康对照者与胰腺癌患者中DNA碱基8-羟基-2'-脱氧鸟苷(8-OHdG)和C反应蛋白(CRP)这两种炎症标志物的水平。材料与方法:从转诊至内镜超声(EUS)中心的患者群体中招募了55例胰腺癌患者和55名健康对照者。采用32P后标记法对外周血细胞的DNA含量进行8-OHdG分析。通过高灵敏度检测法测定血清CRP水平,并从个体病历中收集用于比较的人口统计学数据。结果:与对照组相比,病例组的8-OHdG DNA加合物/106个核苷酸的中位数(四分位间距)和CRP显著升高(相对吸光度值分别为208.8(138.0 - 340.8)对121.8(57.7 - 194.8);P<0.001)以及(3.5(1.5 - 8.6)对0.5(0.2 - 1.5)mg/L;P<0.001)。多个条件回归模型证实胰腺癌与外周白细胞中的氧化性DNA损伤有关。结论:我们的研究结果表明,白细胞8-OHdG加合物作为胰腺癌患者全身氧化性DNA损伤指标的重要性。除了CRP炎症标志物升高外,这支持了炎症在胰腺癌发生中的作用以及癌症发展过程中的炎症反应。