Background: Genome-wide association studies (GWAS) have identified multiple loci associated with epithelial ovarian cancer (EOC) susceptibility, but further progress requires integration of epidemiology and biology to illuminate true risk loci below genome-wide significance levels (P < 5 × 10). Most risk SNPs lie within non-protein-encoding regions, and we hypothesize that long noncoding RNA (lncRNA) genes are enriched at EOC risk regions and represent biologically relevant functional targets.
Methods: Using imputed GWAS data from about 18,000 invasive EOC cases and 34,000 controls of European ancestry, the GENCODE (v19) lncRNA database was used to annotate SNPs from 13,442 lncRNAs for permutation-based enrichment analysis. Tumor expression quantitative trait locus (eQTL) analysis was performed for sub-genome-wide regions (1 × 10 > P > 5 × 10) overlapping lncRNAs.
Results: Of 5,294 EOC-associated SNPs (P < 1.0 × 10), 1,464 (28%) mapped within 53 unique lncRNAs and an additional 3,484 (66%) SNPs were correlated (r > 0.2) with SNPs within 115 lncRNAs. EOC-associated SNPs comprised 130 independent regions, of which 72 (55%) overlapped with lncRNAs, representing a significant enrichment (P = 5.0 × 10) that was more pronounced among a subset of 5,401 lncRNAs with active epigenetic regulation in normal ovarian tissue. EOC-associated lncRNAs and their putative promoters and transcription factors were enriched for biologically relevant pathways and eQTL analysis identified five novel putative risk regions with allele-specific effects on lncRNA gene expression.
Conclusions: lncRNAs are significantly enriched at EOC risk regions, suggesting a mechanistic role for lncRNAs in driving predisposition to EOC.
Impact: lncRNAs represent key candidates for integrative epidemiologic and functional studies. Further research on their biologic role in ovarian cancer is indicated. Cancer Epidemiol Biomarkers Prev; 26(1); 116-25. ©2016 AACR.
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http://dx.doi.org/10.1158/1055-9965.EPI-16-0341 | DOI Listing |
Insights Imaging
January 2025
Medical Research Department, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, P. R. China.
Objective: To develop an automatic segmentation model to delineate the adnexal masses and construct a machine learning model to differentiate between low malignant risk and intermediate-high malignant risk of adnexal masses based on ovarian-adnexal reporting and data system (O-RADS).
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Cancer Res
January 2025
University of Maryland, Baltimore, Baltimore, Maryland, United States.
DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian and other cancers. Here, we showed that combining DNMTis and PARPis upregulates expression of the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction of PMR in mitochondria, serving as a gateway for STING-dependent interferon/inflammasome signaling.
View Article and Find Full Text PDFJ Pediatr Hematol Oncol
January 2025
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX.
Borderline ovarian tumors (BOTs) are rare in pediatric populations and typically follow an indolent clinical course with few reported recurrences. Consequently, guidelines for pediatric BOT management are minimal. We retrospectively examined the management of 15 adolescent patients who underwent BOT resection at our institution over 14 years, with a specific focus on recurrence.
View Article and Find Full Text PDFFood Funct
January 2025
Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
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View Article and Find Full Text PDFDespite recent advances, improvements to long-term survival in metastatic carcinomas, such as pancreatic or ovarian cancer, remain limited. Current therapies suppress growth-promoting biochemical signals, ablate cells expressing tumor-associated antigens, or promote adaptive immunity to tumor neoantigens. However, these approaches are limited by toxicity to normal cells using the same signaling pathways or expressing the same antigens, or by the low frequency of neoantigens in most carcinomas.
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