722 DNA Repair Capacity in Peripheral Blood Lymphocytes of Endometrial Cancer Patients with Family History of Cancer

2012 ◽  
Vol 48 ◽  
pp. S171
Author(s):  
L. Buchynska ◽  
O. Brieieva ◽  
O. Bilyk
2018 ◽  
Vol 40 (1) ◽  
pp. 68-72 ◽  
Author(s):  
L G Buchynska ◽  
O V Brieieva

Background: The development of hormone-dependent cancers, including endometrial carcinomas, in great part may be mediated by the genotoxic effects of estrogen metabolites, among which 4-hydroxyestradiol (4OHE2) is characterized by the most prominent DNA-damaging properties. It is assumed that the individual sensitivity to the 4OHE2 may determine the predisposition to endometrial cancer (EС). Aim: To analyze the sensitivity of peripheral blood lymphocytes (PBLs) of EC patients to the 4OHE2 and to evaluate the repair efficiency of 4OHE2-induced DNA damage. Materials and Methods: The study was performed on the PBLs of 53 EC patients and 20 healthy women. The level of DNA damage was measured using the comet assay and was expressed as % tail DNA. The DNA repair efficiency (%) was evaluated by determining the ratio between the amount of repaired DNA damage and the level of 4OHE2-induced damage that appeared after incubation of PBLs with 4OHE2. Results: In PBLs of EC patients, a higher level of 4OHE2-induced DNA damage (32.0 ± 2.2% tail DNA) and lower DNA repair efficiency (34.0 ± 4.5%) was observed compared to PBLs of healthy women (22.3 ± 2.3% tail DNA and 48.8 ± 4.5%, respectively). PBLs of EC patients with deep tumor invasion of myometrium were characterized by more prominent decrease of DNA repair than those with less invasive tumor (< ½ of myometrium) (20.9 ± 7.8 and 43.7 ± 6.7%, respectively). Furthermore, lower DNA repair efficiency was detected in the PBLs of EC patients with a family history of cancer compared to this parameter in patients with sporadic tumors (20.9±7.8 and 47.1 ± 5.5%, respectively). Conclusion: The PBLs of EC patients are characterized by increased sensitivity to the genotoxic effect of 4OHE2 and reduced repair efficiency regarding 4OHE2-induced DNA damage. A lower level of DNA repair is observed in EC patients with deep tumor myometrial invasion and a family history of cancer.


2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Fatemeh Sadeghi ◽  
Marzieh Asgari ◽  
Mojdeh Matloubi ◽  
Maral Ranjbar ◽  
Nahid Karkhaneh Yousefi ◽  
...  

Abstract Background DNA repair pathways, cell cycle arrest checkpoints, and cell death induction are present in cells to process DNA damage and prevent genomic instability caused by various extrinsic and intrinsic ionizing factors. Mutations in the genes involved in these pathways enhances the ionizing radiation sensitivity, reduces the individual’s capacity to repair DNA damages, and subsequently increases susceptibility to tumorigenesis. Body BRCA1 and BRCA2 are two highly penetrant genes involved in the inherited breast cancer and contribute to different DNA damage pathways and cell cycle and apoptosis cascades. Mutations in these genes have been associated with hypersensitivity and genetic instability as well as manifesting severe radiotherapy complications in breast cancer patients. The genomic instability and DNA repair capacity of breast cancer patients with BRCA1/2 mutations have been analyzed in different studies using a variety of assays, including micronucleus assay, comet assay, chromosomal assay, colony-forming assay, γ -H2AX and 53BP1 biomarkers, and fluorescence in situ hybridization. The majority of studies confirmed the enhanced spontaneous & radiation-induced radiosensitivity of breast cancer patients compared to healthy controls. Using G2 micronucleus assay and G2 chromosomal assay, most studies have reported the lymphocyte of healthy carriers with BRCA1 mutation are hypersensitive to invitro ionizing radiation compared to non-carriers without a history of breast cancer. However, it seems this approach is not likely to be useful to distinguish the BRCA carriers from non-carrier with familial history of breast cancer. Conclusion In overall, breast cancer patients are more radiosensitive compared to healthy control; however, inconsistent results exist about the ability of current radiosensitive techniques in screening BRCA1/2 carriers or those susceptible to radiotherapy complications. Therefore, developing further radiosensitivity assay is still warranted to evaluate the DNA repair capacity of individuals with BRCA1/2 mutations and serve as a predictive factor for increased risk of cancer mainly in the relatives of breast cancer patients. Moreover, it can provide more evidence about who is susceptible to manifest severe complication after radiotherapy.


2017 ◽  
Vol 39 (4) ◽  
pp. 299-303 ◽  
Author(s):  
L G Buchynska ◽  
O V Brieieva ◽  
N P Iurchenko ◽  
V V Protsenko ◽  
S V Nespryadko

To date, genome instability is considered to be a common feature not only of tumor cells, but also of non-malignant cells of cancer patients, including peripheral blood lymphocytes (PBLs). The issue of the association between genome instability in tumor cells and PBLs, as well as of its relationship with tumor progression remains poorly understood. Aim: To evaluate the level DNA damage in tumor cells and PBLs of endometrial cancer (EC) patients with regard to clinical and morphological characteristics of the patients. Materials and Methods: DNA damage was assessed in 106 PBLs samples and 42 samples of tumor cell suspension from EC patients by comet assay. PBLs from 30 healthy women were used as control. The level of DNA damage was expressed as the percentage of DNA in the comet tails (% tail DNA). Results: It was revealed that the amount of DNA damage in PBLs of EC patients was 2.2 times higher in comparison with that of healthy donors (8.3 ± 0.7 and 3.7 ± 0.4% tail DNA, respectively) (p < 0.05). In this study, no association between the levels of DNA damage in endometrial tumor cells and PBLs was observed (r = 0.11; p > 0.05). The amounts of DNA damage both in tumor cells and PBLs were not related to the degree of tumor differentiation as well as the depth of myometrial invasion, but depended on the body mass index (BMI) of EC patients: high level of lesions was observed in patients with elevated BMI values. Furthermore, the level of DNA damage in tumor cells was associated to familial aggregation of cancer and was significantly higher in endometrial cells from patients with family history of cancer vs that from EC patients with sporadic tumors (32.3 ± 2.9 and 22.8 ± 1.8% tail DNA, respectively) (p < 0.05). It was also found that for women who had high level of DNA damage in PBLs, the risk of EC was greater (odds ratio value of 3.5) compared to those with low level of such lesions. Conclusion: Genome instability that appears as an increased level of DNA damage in tumor cells and PBLs of EC patients is associated with BMI and family history of cancer and can reflect a predisposition to cancer.


2020 ◽  
Vol 3 (2) ◽  
pp. 66
Author(s):  
Nihal Sofyan ◽  
I Ketut Sudiana ◽  
Brahmana Askandar

Introduction: Endometrial cancer is a malignant tumor of primary endometrial epithelium that placed as the sixth most common cancer in women worldwide. The exact cause of it is still unknown although there are several risk factors has been well studied and the incidence rate is increasing every year. The aim of the study is to describe the profile of endometrial cancer patients in third referral hospital in Surabaya based on known risk factors.Methods: We collected data retrospectively through the medical record of outpatients with endometrial cancer diagnosis from January-December 2016. A total of 120 patients were collected and only 95 patients who meet the inclusion criteria. Data about age, age of menarche, status of menopause, parity, Body Mass Index (BMI), history of disease, and family history of cancer were extracted then presented descriptively.Results: From 95 patients, the largest distribution were age 51-60 years old (47,37%), and was diagnosed mostly in women with parity ≤2 (47,37%), postmenopausal status (61,05%), age of menarche ≥ 12 (85,26%), and normal weight (35,79%). Most of patients didn’t have either any history of disease (57,89%) or family history of cancer (89,47%).Conclusion: Most of the endometrial cancer patients in Dr. Soetomo General hospital Surabaya were women aged 51-60 years old with postmenopausal status, age of menarche ≥ 12 years old, number of parities ≤2, and normal weight. The majority of them were also found to have no history of disease and family history of cancer.


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