Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Maternal-neonatal 8-hydroxy-deoxyguanosine serum concentrations as an index of DNA oxidation in association with the mode of labour and delivery

Aim. To investigate the effect of the mode of labour and delivery on the total antioxidant status (TAS), and the biomarker of DNA oxidation, 8-hydroxy-deoxyguanosine (8-OHdG) serum levels, in mothers and their newborns. Subjects and methods. Some 106 women with normal pregnancy and normal blood biochemical parameters were divided into 4 groups: Group A ( n = 28) with normal labour and vaginal delivery ( VG), Group B ( n = 25) with scheduled cesarean section ( CS), Group C ( n = 26) with ‘emergency’ CS, and Group D ( n = 27) with prolonged labour + VG. Blood was obtained fr? m the mothers at the beginning of labour, and immediately after delivery ( pre- and post-delivery), as well as from the umbilical cord ( CB). TAS, 8-OHdG and creatine kinase (CK) were measured in the sera with appropriate methodology. Results. TAS levels were almost similar in all the groups pre- delivery, and in CB irrespective of the mode of labour and delivery, and remarkably decreased in Groups C and D post-delivery. 8-OHdG levels in Group C ( 0.94 +/- 0.08 ng/ml) and Group D (0.98 +/- 0.08 ng/ml) were significantly higher than those in Group A (0.26 +/- 0.01 ng/ml, p < 0.001) and Group B (0.28 +/- 0.07 ng/ml, p < 0.001) post-delivery. 8-OHdG levels were low in CB, independent of the mode of labour. CK positively correlated with 8-OHdG ( r = 0.48, p < 0.001), the latter negatively correlated with TAS ( r = - 0.53, p < 0.01). Conclusions. The lowest TAS and the highest 8-OHdG levels were found in Groups C and D post-delivery, probably due to the long-term participation of the mothers’ skeletal and uterus muscles, whereas 8-OHdG levels were low in CB irrespective of the mode of delivery, possibly as a consequence of the antioxidant action of the placenta and/or the low lipid levels in the serum of the umbilical cord

Bioanalytical LC-MS Method for the Quantification of Plasma Androgens and Androgen Glucuronides in Breast Cancer

The physiological and pathological development of the breast is strongly affected by the hormonal milieu consisting of steroid hormones. Mass spectrometry (MS) technologies of high sensitivity and specificity enable the quantification of androgens and consequently the characterization of the hormonal status. The aim of this study is the assessment of plasma androgens and androgen glucuronides, in the par excellence hormone-sensitive tissue of the breast, through the application of liquid chromatography-mass spectrometry (LC-MS). A simple and efficient fit-for-purpose method for the simultaneous identification and quantification of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), androsterone glucuronide (ADTG) and androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) in human plasma was developed and validated. The presented method permits omission of derivatization, requires a single solid-phase extraction procedure and the chromatographic separation can be achieved on a single C18 analytical column, for all four analytes. The validated method was successfully applied for the analysis of 191 human plasma samples from postmenopausal women with benign breast disease (BBD), lobular neoplasia (LN), ductal carcinoma in situ and invasive ductal carcinoma (IDC). DHEAS plasma levels exhibited significant differences between LN, IDC and BBD patients (P < 0.05). Additionally, ADTG levels were significantly higher in patients with LN compared with those with BBD (P < 0.05)