Pancreatic Cancer is Associated with Peripheral Leukocyte Oxidative DNA Damage

Mohamadkhani, Ashraf; Pourshams, Akram; Viti, Jessica; Cellai, Filippo; Mortazavi, Kamran; Sharafkhah, Maryam; Sotoudeh, Masoud; Malekzadeh, Reza; Boffetta, Paolo; Peluso, Marco

doi:10.22034/APJCP.2017.18.5.1349

Pancreatic Cancer is Associated with Peripheral Leukocyte Oxidative DNA Damage

Document Type : Research Articles

Authors

¹ Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

² Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

³ Cancer Risk Factor Branch, Cancer Prevention Laboratory, Cancer Research and Prevention Institute (ISPO), Via Cosimo il Vecchio 2, 50139, Florence, Italy.

⁴ Department of Epidemiology and Biostatistics, Tehran University of Medical Sciences, Tehran, Iran.

⁵ Tisch Cancer Institute, Mount Sinai School of Medicine, New York, USA.

10.22034/APJCP.2017.18.5.1349

Abstract

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.

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