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Background Exposure to pesticides is associated with an increase in the incidence of cancer. We aimed to investigate the association of serum organochlorine pesticides (OCPs) and organophosphorus pesticides (OPs) levels and GSTM1/GSTT1 gene polymorphism with bladder cancer (BC). Methods This study was performed on 57 patients with BC and 30 controls (C). Acetylcholinesterase (AChE) activity, arylesterase activity of paraoxonase‐1 (ARE), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels were determined in serums of all participants. Genomic DNA was extracted using the salting out method and GSTM1/GSTT1 gene polymorphisms were examined by multiplex polymerase chain reaction assay. Measurement of OCPs (α‐hexachlorocyclohexane [α‐HCH], β‐HCH, γ‐HCH, 2,4‐dichlorodiphenyltrichloroethane [2,4‐DDT], 4,4‐DDT, 2,4‐ dichlorodiphenyldichloroethylene [2,4‐DDE], and 4,4‐DDE) in serum was carried out using an FID‐equipped gas‐chromatography system. Results AChE activity was significantly lower, ARE activity and TAC were declined but it was not statistically significant, however, α‐HCH, γ‐HCH, 4,4‐DDE, 2,4‐DDT, and 4,4‐DDT pesticides, and MDA were significantly higher in BC patients compared with the control subjects. Also, a positive correlation was found between the number of smoked cigarettes and the years of smoking with BC development. There was no association between GSTM1/GSTT1 gene polymorphisms and OCPs in BC patients. Conclusion Due to the higher levels of some OCPs in the BC patients, along with the reduction in AChE activity and increased MDA levels, it may be concluded that OCPs and OPs play an important role in the induction of BC in southeastern Iran.

Background: Oxidative stress is associated with the development of a large variety of malignancies. Objectives: This study was conducted to evaluate the acetylcholinesterase (AChE) and arylesterase (ARE) activities, malondialdehyde (MDA), and total antioxidant capacity (TAC) plasma levels in two groups of patient with breast cancer and benign breast diseases compared to healthy volunteers. Methods: The present study was composed of two groups of patients with malignant breast tumors (MBT) and benign breast diseases (BBD), and a control group (CON). Enzyme activities and antioxidants markers were measured, using spectrophotometry. Results: In both case groups, MBT and BBD, ARE was found to show lower activity compared to CON group (P = 0.004 and P = 0.014, respectively). Lower activity of AChE was found in both MBT and BBD compared to CON subjects (P = 0.003 and P = 0.034, respectively). The mean plasma levels of MDA in both groups of patients MBT and BBD were higher than those in CON (P < 0.001 for both comparisons). No significant differences were detected between groups regarding the mean levels of TAC. Conclusions:The results obtained from the current study indicate that healthy subjects show a different redox status than patients with MBT and BBD. Our data suggest that erythrocyte AChE may be considered as an indicator of oxidative stress along with other factors in patients with breast tumors. Thus, consuming antioxidant supplements can be helpful for the prevention of breast diseases.

Aberrant patterns in promoter methylation of tumor-suppressor genes and posttranslational modifications of histone proteins are considered as major features of malignancy. In this study, we aimed to investigate promoter methylation of three tumor-suppressor genes (BRCA-1, MGMT, and P16) and three histone marks (H3K9ac, H3K18ac, and H4K20me3) in patients with breast tumors. This case-control study included 27 patients with malignant breast tumors (MBT) and 31 patients with benign breast tumors (BBT). The methylation-specific PCR was used for determining promoter methylation of BRCA-1, MGMT, and P16 genes. Western blot analysis was performed to detect histone lysine acetylation (H3K9ac and H3K18ac) and lysine methylation (H4K20me3). BRCA-1 promoter methylation was detected in 44.4% of the MBT whereas this alteration was found in 9.7% of BBT (P = 0.005). The Kaplan-Meier analysis indicated that hypermethylation in BRCA-1 promoter was significantly associated with poor overall survival of patients with breast cancer (P = 0.039). MGMT promoter methylation was identified in 18.5% of MBT and 0.0% of the BBT (P = 0.01). The frequency of P16 promoter methylation was 25.8% in BBT and 11.1% in MBT (P = 0.12). As compared with BBT, MBT samples displayed the aberrant patterns of histones marks with hypomethylation of H4K20 and hypoacetylation of H3K18 (P = 0.03 and P = 0.04, respectively). There was a negative significant correlation between H3K9ac levels and tumor size in MBT group (r = −0.672; P = 0.008). The present findings suggest that promoter hypermethylation of MGMT and BRCA-1 genes along with alterations in H3K18ac and H4K20me3 levels may have prognostic values in patients with breast cancer. Moreover, the detection of these epigenetic modifications in breast tumors could be helpful in finding new methods for breast cancer therapy. K E Y W O R D S breast cancer, breast tumor, epigenetic, histone modification, promoter methylation, tumor suppressor J Cell Biochem. 2019;120:13726-13736. wileyonlinelibrary.com/journal/jcb 13726 |

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