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

Association between endometrial microbiome and implantation success in women with frozen embryo transfer: results of a prospective cohort study

AbstractThe aim of this prospective study was to compare the endometrial microbiome between pregnant and non-pregnant women after frozen embryo transfer (FET) with euploid embryos. Endometrial biopsies were collected from 30 women during the mid-luteal phase in a natural cycle. FET was performed with euploid embryos up to 3 months after the biopsy. Endometrial microbiota composition was analysed using 16S rRNA (v4-v5 region) next generation sequencing (NGS). The analysis of different clinical outcomes after the biopsy (no pregnancy (n = 14), and ultrasound confirmed pregnancy (n = 16)) revealed differences in the endometrial microbiome composition. In total, 271 distinct bacterial species and 668 bacterial genera were identified. The number of unique species found in non-pregnant women was 62 (22.88%), while in the patients who became pregnant after FET it was 39 (14.39%). Among them, bacteria with high frequency of occurrence such as Bacteroides spp., Cutibacterium granulosum, Isoptericola spp., Acetomicrobium spp., Marivivens spp. and Syntrophomonas spp. were found only in non-pregnant patients, while Bosea spp. was present only in pregnant women. The analysis of bacteria relative abundance revealed that Lactobacillus genus was not significantly different between the studied groups. In contrast, Serratia marcescens, Staphylococcus spp., Glutamicibacter spp. and Delftia spp. were significantly enriched in the non-pregnant group. In conclusion, specific bacteria taxa had higher relative abundance in the endometrium of patients with implantation failure after FET with euploid embryos. We hypothesize that an appropriate treatment for optimization of endometrial microbiome content in women with diagnosed microbiome dysbiosis could be beneficial for improvement of pregnancy rates

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