Dehydroepiandrosterone Modulates Oxidative Dna Damage in Pancreatic Cancer: A Case–Control Study Publisher



Fazli HR¹ ; Mohamadkhani A² ; Godarzi HR¹ ; Pourshams A² ; Jafari Nia M³
Source: JGH Open Published:2021

Abstract

Background and Aim: Dehydroepiandrosterone (DHEA) has a protective role against several types of cancer, although its mechanisms of action are still unknown, it may be related to the antioxidant effect of DHEA. We hypothesized that DHEA has a preventive effect on the formation of the 8-hydroxy-2′-deoxyguanosine (8-OHdG) DNA adduct in pancreatic cancer patients. Methods: Serum DHEAs were quantified by the ELISA method in 50 pancreatic cancer patients with histopathological diagnosis of adenocarcinoma and 50 matched controls. The amount of 8-OHdG was assessed in peripheral blood leukocyte extracted DNA using a 32P-DNA postlabeling technique. Results: Pancreatic cancer patients had lower serum DHEA levels than healthy controls, although it did not differ significantly. Instead, the 8-OHdG DNA adduct was significantly higher in the case than in the control (P = <0.001). Remarkably, the negative correlation between 8-OHdG and DHEA was distinguished between cases (P = 0.025, r = −0.315) but not in controls (P = 0.078, r = −0.250). In the crude and corrected estimate for pancreatic cancer risk, a significant protective effect of DHEA against pancreatic cancer was found with increasing DHEA when 8-OHdG is greater than its median (adjusted OR = 0, 79, 95% confidence intervals [CI]: 0.66–0.94). Similarly, a lower risk of pancreatic cancer was observed in the third tertile of DHEA (adjusted OR = 0.05, 95% CI: 0.004–0.69). Conclusions: These results indicate that serum DHEA reduces the risk of pancreatic cancer with an anti-DNA damage effect. Hence, the influence of DHEA to prohibit the accumulation of 8-OHdG may be one of its physiological functions. © 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.