Publications by authors named "Denise G O'Mahony"
Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS.
View Article and Find Full Text PDFArticle Synopsis
- Clinical genetic testing helps find cancer risks by identifying gene changes, but some of these changes are confusing because we don't know what they mean (called VUS).
- Researchers studied a huge number of breast cancer patients and healthy people to understand these confusing gene changes better.
- They found that their method of analyzing data closely matches what other experts say about which gene changes are harmless or harmful, giving more information about 785 unclear changes.
Article Synopsis
- The study investigates how common genetic variants related to breast cancer and other traits affect the immune environment in tumors (TIME) and responses to treatment.
- Researchers analyzed immune features from breast tumor samples and adjacent normal tissues of 825 breast cancer patients, identifying links between genetic risk scores and immune traits.
- Key findings include inverse relationships between genetic risk scores for inflammatory diseases and immune signaling, alongside positive associations for certain cell types, highlighting the connection between genetics and tumor immunity.
It is estimated that around 5% of breast cancer cases carry pathogenic variants in established breast cancer susceptibility genes. However, the underlying prevalence and gene-specific population risk estimates in Cyprus are currently unknown. We performed sequencing on a population-based case-control study of 990 breast cancer cases and 1094 controls from Cyprus using the BRIDGES sequencing panel.
View Article and Find Full Text PDFBackground: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.
Methods: Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies.
Article Synopsis
- Many variants found in disease susceptibility genes are classified as variants of uncertain significance (VUS), making their interpretation critical for clinical decisions.
- This study introduces a new likelihood ratio-based method that takes into account gene-specific age-related penetrance to better analyze the pathogenicity of these variants.
- The method outperformed traditional approaches in simulated and real datasets, allowing for clearer classifications of variants as pathogenic or non-pathogenic for conditions like breast cancer, and includes user-friendly tools for researchers.