Dehydroepiandrosterone modulates oxidative DNA damage in pancreatic cancer: A case-control study.

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.