The association between polymorphisms of the RAD51-G135C, XRCC2-Arg188His and XRCC3-Thr241Met genes and clinico-pathologic features in breast cancer in Poland.

BACKGROUND: XRCC2 and XRCC3 genes are structurally and functionally related to RAD51 which plays an important role in homologous recombination, the process frequently involved in cancer transformation. MATERIAL AND METHODS: In the present work the distribution of genotypes and frequency of alleles of the RAD51 G135C polymorphism, XRCC2 Arg 188His and XRCC3 Thr241Met polymorphism in 790 cases of breast cancer were investigated. The control group consisted of 798 cancer-free blood donors (age +/- 5 years) who were sex and ethnicity-matched. The polymorphisms were determined by PCR-RFLP methods. We also correlated genotypes with the clinical characteristics of breast cancer patients. RESULTS: Our results obtained for the 135G>C polymorphism of the RAD51 gene indicated that both the C/C genotype and the C allele are strongly associated with breast cancer. The Arg/His genotype of XRCC2 (OR = 2.16, 95% CI = 1.48-3.16) and Thr/Met of XRCC3 increased the risk of type I breast cancer occurrence (OR = 2.33, 95% CI = 1.60-3.41). We did not find any association with the RAD51, XRCC2/3 gene polymorphism and estrogen and progesterone receptor status. CONCLUSION: The results support the hypothesis that the polymorphism of RAD51 and XRCC2/3 gene may be associated with the incidence of sporadic breast cancer in Polish women.

Similar PAI-1 expression in visceral and subcutaneous fat of postmenopausal women.

Recent studies showed that intraabdominal visceral fat located in the mesenterium and omentum may significantly influence the circulating plasminogen activator inhibitor type 1 (PAI-1). To substantiate this link, we performed analysis of PAI-1 expression in human visceral and subcutaneous adipose tissues in peri- and postmenopausal women. The samples of both visceral and subcutaneous fat from 28 generally healthy women (aged 45-69 years) with a wide range of body mass index (BMI; 22.30-38.67 kg/m2), who underwent surgical operation due to benign ovary and uterine tumours, were obtained. In these samples, expression of mRNAs for PAI-1, tumour necrosis factor alpha (TNFalpha), acyl-CoA synthetase (ACS), and glucose transporter (GLUT-4) was analysed by relative quantitative RT PCR and correlated with plasma PAI-1 antigen. In addition, visceral fat area was measured with computer tomography. Both types of fat tissues contained similar quantities of PAI-1 mRNA, and there was no correlation between plasma PAI-1, measured both by antigen and activity, with either visceral or subcutaneous fat PAI-1 mRNA. Furthermore, there was no significant association between the expression of PAI-1 mRNA and TNFalpha mRNA in tested fat samples. PAI-1 mRNA in both fat tissues was significantly correlated with plasma levels of estradiol (positive correlation) and follicle-stimulating hormone (FSH; negative correlation). Finally, the expression of PAI-1 mRNA was negatively correlated with mRNA of ACS present in both fat tissues. In summary, this study directly indicates that PAI-1 mRNA is similarly expressed in both subcutaneous and visceral fat of peri- and postmenopausal women and its expression strongly depends upon lipid metabolism.

[The influence of hormone replacement therapy containing transdermal 17-beta estradiol and oral medroxyprogesterone acetate on coagulation and fibrinolysis]. / Wplyw hormonalnej terapii zastepczej pod postacia przezskórnego 17 beta-estradiolu wraz ze stosowanym doustnie octanem medroksyprogesteronu na uklad krzepniecia i fibrynolizy.

OBJECTIVE: The aim of the study was to evaluate some coagulative and fibrinolytic changes in women taking hormone replacement therapy (HRT). MATERIALS AND METHODS: In 29 women aged 45-64 years with osteoporosis and climacteric symptoms several fibrinolytic and coagulative parameters were measured. These measurements were performed three times in each women--before and after three and six months of HRT containing transdermal 17 beta-estradiol (50 mg per day) and oral medroxyprogesterone acetate (2.5 mg per day). RESULTS: PAI-1 (antigen) and factor VII (activity) were decreased significantly during the trial. No other significant modifications in the examined parameters (fibrinogen, antithrombin III, protein C, protein S, thrombin-antithormbin III complexes, t-PA and D-dimers) were detected. CONCLUSIONS: The hormone replacement therapy can reduce the risk of coronary heart disease thanks to decreased levels of PAI-1 and factor VII. No other changes in coagulation and fibrinolysis were observed during the treatment.

[Assessment of fat tissue distribution impact on selected prothrombin and fibrinolytic factors in pre- and postmenopausal women]. / Ocena wplywu typu rozmieszczenia tkanki tluszczowej na wybrane parametry ukladu krzepniecia i fibrynolizy u kobiet w okresie pre- i pomenopauzalnym.

OBJECTIVES: Objective was to examine the relationship of obesity, body fat distribution fasting plasma insulin concentrations and triglycerides of pro-thrombotic and fibrinolitics factors in pre and postmenopausal women. MATERIAL AND METHODS: We assessed 24 (13 nonobese and 11 obese) postmenopausal and 44 (15 obese and 29 non obese) premenopausal women. Plasma concentration of PAI-1 ag,PAI-1 activity, fibrinogen, tPA-1 akt, tPA ag, von Willebrand factor, fasting plasma insulin, and the lipid pattern (cholesterol, TG, HDL, LDL) was measured. The body fat distribution was assessed by waist-to-hip circumference measuring. RESULTS: Postmenopausal subjects had higher PAI-1 act. and PAI-1 ag (p < 0.05 and 0.001 respectively), vWf and lower ATIII. There was direct correlation between PAI-1 act., Fibrinogen and BMI in both groups of patients together and in premenopausal group PAI-1 act correlated directly and tPA ag/act. indirectly with plasma insulin concentrations. CONCLUSIONS: Plasma concentrations of the pro-thrombotic factors are increased in obese and postmenopausal women and correlate directly with BMI and indirectly with plasma insulin concentrations. Plasma concentrations of anti thrombotic factors indirectly correlated with WHR and with plasma insulin concentrations.

[Evaluation of coagulation and fibrinolysis systems in women at peri- and postmenopausal age qualified for hormone replacement therapy]. / Ocena ukladu krzepniecia i fibrynolizy u kobiet w okresie okolo- i pomenopauzalnym kwalifikowanych do hormonoterapii zastepczej.

OBJECTIVE: The aim of the study was to evaluate coagulation and fibrinolysis systems in peri- and postmenopausal women who were qualified for hormone replacement therapy. MATERIALS AND METHODS: In sixty eight peri- and postmenopausal women qualified for hormone replacement therapy under study some coagulation and fibrinolysis parameters were measured in serum--platelet count, prothrombin time, prothrombin ratio, INR, APTT, thrombin time (TT), fibrinogen, D-dimers, TAT, factor VII, activity of antithrombin III, activity of protein C and protein S, PAI-1 and t-PA concentration. Controls were 26 healthy, reproductive women. RESULTS: Out of fifteen examined coagulation and fibrinolysis parameters in six cases there were statistically significant differences between menopausal women and controls:--APTT and TT were shortened (but within normal range) in menopausal group than in controls;--concentration of fibrinogen in menopausal group (also within normal range) was higher than in controls;--activity of factor VII was risen (and outside normal range) in the examined group in comparison to the controls;--activity of protein S was lower in menopausal than in reproductive women;--also concentration of t-PA was lower in the examined group. CONCLUSIONS: 1. Differences in the values of coagulation and fibrinolytic parameters between the menopausal and reproductive groups of women may testify to the increased risk of thrombus formation in women at peri- and postmenopausal age. 2. Impaired fibrinolysis (low t-PA, high PAI-1) together with the rise in activity of factor VII can contribute to the development of ischaemic heart disease in menopausal women.

[Clinical and histopathologic picture of lichen sclerosus treated with clobetasol propionate]. / Obraz kliniczny i histopatologiczny liszaja twardzinowego sromu w trakcie leczenia propionianem klobetazolu.

Effects of treating of the vulvar lichen scleroses by topical using of clobetasol propionate. The period of observation was 1 year. All patients showed clinical improvement or full regression depending on the period of disease. In all cases histopathologic examination was performed.

Hemostatic variables, carbohydrate metabolism and lipid profile in women with low body mass index.

The aim of this study was to evaluate hemostatic variables in women according to different body mass index (BMI) values, and then correlate them with some metabolic parameters - fasting insulin and glucose, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Eighty-four female patients aged 18-39 years were recruited, and agreed to participate in the study. The study group was divided into three subgroups according to BMI: low BMI (BMI < 18.5 kg/m2; n = 43), normal-weight (control) (BMI 18.5-24.99 kg/m2; n = 21) and overweight/obese (BMI > 25 kg/m2; n = 20). BMI was calculated, and the following measurements were taken: International Normalized Ratio, antithrombin III, tissue plasminogen activator (t-PA) activity, t-PA-antigen, plasma fibrinogen level, factor VII, Plasminogen activator inhibitor (PAI)-1 activity and antigen and metabolic parameters: fasting insulin and glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides. The results were statistically analyzed. In the low BMI group, a negative correlation between fasting insulin and PAI-1 activity, and a positive correlation between fasting glucose and PAI-1 antigen were observed. Also, a strong negative correlation between PAI-1 activity and insulin/glucose index was found. Plasma insulin levels were significantly lower in the low-BMI women than in the overweight/obese group (p < 0.001) and with no difference compared to the control group. We did not find any difference in fasting glucose level between all groups. HDL-cholesterol showed the highest levels in the normal BMI group and was significantly higher than in the low BMI and obese groups (p < 0.05 and p < 0.01, respectively). PAI-1 activity in the low BMI women revealed increased activity in comparison to control and overweight/obese women (p < 0.001 and p < 0.05, respectively). Lower antigen levels were also shown as compared to both these groups (p < 0.001 and p < 0.001, respectively). Similar results were obtained with t-PA antigen levels (p < 0.001 and p < 0.001, respectively). There were no differences in activity of t-PA in all groups. Obese women showed significantly higher fibrinogen levels than other BMI groups (p < 0.001 and p < 0.001 respectively). Analysis of hemostatic variables in women with a low BMI testify to the impaired fibrinolysis in this group, also showing a strong correlation with carbohydrate metabolism.