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.

Report of limb girdle muscular dystrophy type 2a in 6 Iranian patients, one with a novel deletion in CAPN3 gene.

Calpain3 is a calcium-dependent intracellular protease involved in an autosomal recessive form of muscular dystrophy known as limb-girdle muscular dystrophy type 2A. Many pathogenic mutations have been identified in calpain3, encoded by the CAPN3 gene, which leads to weakness of the pelvic and shoulder girdle muscles. In the present study, whole exome sequencing was performed on six unrelated Iranian families who presented with progressive muscle weakness, with a strong suspicion of Calpainopathies. Genetic analysis of CAPN3 gene revealed five causative variants which had not been reported in the Iranian population before including a novel 6 bp deletion (c.795_800delCATTGA) and four previously reported mutations (c.1939G > T, c.2243G > A, c.2257delGinsAA, and c.2380 + 2T > G). Our findings indicate that exome sequencing can be a very effective and affordable method to diagnose heterogeneous muscular dystrophies, especially in consanguineous populations such as Iran.