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

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.

Insulin‐like growth factor 1 and dehydroepiandrosterone levels in alcoholic liver cirrhosis

“…both sexes itself by directly or indirectly enhancing protein synthesis, muscle growth, and muscle strength. 10,11 Our results confirm that IGF-1 is indeed decreased in LC patients. In the case of DHEA, we expected this hormone to be decreased too, as it was demonstrated, for example, in hepatitis C fibrosis.…”

“…DHEA was chosen as a steroid that is not only a progenitor of male and female sex hormones alike, but that also acts as an anabolic hormone in both sexes itself by directly or indirectly enhancing protein synthesis, muscle growth, and muscle strength. 10 , 11 …”

“…In this study, we tested that hypothesis on two exemplary hormones: IGF‐1 was chosen as a peptide that is unrelated to sex hormones. DHEA was chosen as a steroid that is not only a progenitor of male and female sex hormones alike, but that also acts as an anabolic hormone in both sexes itself by directly or indirectly enhancing protein synthesis, muscle growth, and muscle strength 10,11 …”

DHEA down-regulates mitochondrial dynamics and promotes apoptosis of lung adenocarcinoma cells through FASTKD2

“…All studies have shown that exogenous DHEA supplements have multiple positive effects, including anti-obesity, anti-atherosclerosis, lower blood glucose levels, and enhanced memory 12 . In animal experiments, DHEA can also inhibit the occurrence of chemically induced pancreatic cancer 13 , breast cancer 14 , lung cancer 15 , liver cancer 16 and colon cancers 17 , as well as the occurrence of spontaneous tumors in p53 deficient mice, and inhibit the growth of many cancer cell lines in vitro. DHEA has many protective effects, yet many of these mechanisms remain unclear.…”

Insights into Organochlorine Pesticides Exposure in the Development of Cardiovascular Diseases: A Systematic Review

“…4,8,9 Increased use of pesticides primarily in agriculture and community health is associated with increased risks of human exposure to pesticides accompanying various human diseases, including cancer, neurodegenerative diseases, autism, diabetes, obesity and cardiovascular disease (CVD). 3,[10][11][12] High exposure to pesticides causes oxidative cellular damage stress and metabolic disorder such as hyperlipidemia and, in the long term, CVD. 10,13 For example, higher prevalence rates of diabetes and circulatory system diseases and coronary heart disease are found in people who work in factories producing herbicides and chlorophenol.…”