Publications by authors named "Eccles D"
Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.
Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.
Background: Multiple sclerosis (MS) is a demyelinating autoimmune condition, in which body image may be altered due to a range of biopsychosocial factors. The aim of this review was to examine whether there is a relationship between body image and psychological outcomes in MS, in order to guide clinical intervention development.
Methods: PsycINFO, Medline, CINAHL and Scopus databases were searched systematically in November 2023 for eligible studies, using terms relating to MS and body image.
Purpose: Second primary cancer (SPC) risks after breast cancer (BC) in pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records.
Methods: We followed 25,811 females and 480 males diagnosed with BC and tested for germline PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020.
Background: For female patients with Lynch syndrome (LS), endometrial cancer (EC) is often their first cancer diagnosis. A testing pathway of somatic tumour testing triage followed by germline mismatch repair (MMR) gene testing is an effective way of identifying the estimated 3% of EC caused by LS.
Methods: A retrospective national population-based observational study was conducted using comprehensive national data collections of functional, somatic and germline MMR tests available via the English National Cancer Registration Dataset.
Background: Lynch syndrome carriers ('carriers') are presented with complex, emotionally laden choices regarding management of increased genetic cancer risks. Decision aids encourage active involvement in values-based health decisions. This paper aimed to address the research question: How do Lynch syndrome carriers make sense of their chances of developing cancer, and what are the implications for providing support with decision making about genetic cancer risk management?
Methods: Adult carriers were recruited through a genetics service or involvement with Lynch Syndrome UK.
Clinical Impact of Constitutional Genomic Testing on Current Breast Cancer Care.
Clin Oncol (R Coll Radiol)
August 2024
The most commonly diagnosed cancer in women worldwide is cancer of the breast. Up to 20% of familial cases are attributable to pathogenic mutations in high-penetrance (BReast CAncer gene 1 [BRCA1], BRCA2, tumor protein p53 [TP53], partner and localizer of breast cancer 2 [PALB2]) or moderate-penetrance (checkpoint kinase 2 [CHEK2], Ataxia-telangiectasia mutated [ATM], RAD51C, RAD51D) breast-cancer-predisposing genes. Most of the breast-cancer-predisposing genes are involved in DNA damage repair via homologous recombination pathways.
View Article and Find Full Text PDFObjectives: To report the long-term outcomes from a longitudinal psychosocial study that forms part of the 'Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls' (IMPACT) study. The IMPACT study is a multi-national study of targeted prostate cancer (PrCa) screening in individuals with a known germline pathogenic variant (GPV) in either the BReast CAncer gene 1 (BRCA1) or the BReast CAncer gene 2 (BRCA2).
Subjects And Methods: Participants enrolled in the IMPACT study were invited to complete a psychosocial questionnaire prior to each annual screening visit for a minimum of 5 years.
Background: The CanRisk tool, which operationalises the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is used by Clinical Geneticists, Genetic Counsellors, Breast Oncologists, Surgeons and Family History Nurses for breast cancer risk assessments both nationally and internationally. There are currently no guidelines with respect to the day-to-day clinical application of CanRisk and differing inputs to the model can result in different recommendations for practice.
Methods: To address this gap, the UK Cancer Genetics Group in collaboration with the Association of Breast Surgery and the CanGene-CanVar programme held a workshop on 16 of May 2023, with the aim of establishing best practice guidelines.
Background: Fast adaptation of glycolytic and mitochondrial energy pathways to changes in the tumour microenvironment is a hallmark of cancer. Purely glycolytic ρ tumour cells do not form primary tumours unless they acquire healthy mitochondria from their micro-environment. Here we explored the effects of severely compromised respiration on the metastatic capability of 4T1 mouse breast cancer cells.
View Article and Find Full Text PDFBackground: Second primary cancers (SPCs) after breast cancer (BC) present an increasing public health burden, with little existing research on socio-demographic, tumour, and treatment effects. We addressed this in the largest BC survivor cohort to date, using a novel linkage of National Disease Registration Service datasets.
Methods: The cohort included 581,403 female and 3562 male BC survivors diagnosed between 1995 and 2019.
To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10).
View Article and Find Full Text PDFArticle Synopsis
- The research focuses on creating a Patient Decision Aid (PtDA) called Lynch Choices, specifically designed for families dealing with Lynch Syndrome, a genetic cancer susceptibility.
- Involving both patients and an international panel of stakeholders, the project emphasizes co-designing the PtDA to ensure it meets user needs by incorporating multimedia, clearer risk presentation, and improving accessibility.
- The study highlights that simply developing a PtDA isn't enough; effective implementation in clinical settings is crucial to make the tool beneficial for patients and clinicians, and future assessments will measure its real-world use and impact.
The 313-variant polygenic risk score (PRS) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank.
View Article and Find Full Text PDFBackground: Many cancer survivors following primary treatment have prolonged poor quality of life.
Aim: To determine the effectiveness of a bespoke digital intervention to support cancer survivors.
Design: Pragmatic parallel open randomised trial.
Article Synopsis
- The study examines the integration of genomic data across NHS laboratories in England and Wales, highlighting variations in data structure, quality, and ease of local assembly for cancer susceptibility gene testing.
- A survey of 51 clinical scientists revealed significant differences in how variant data is transferred, formatted, and classified within Laboratory Information Management Systems (LIMS) across the participating labs.
- The findings indicate that current workflows are often inefficient and prone to errors due to their manual nature, suggesting that implementing recommended improvements could streamline data submission processes for better national and international collaboration.
Background: Testing for germline pathogenic variants (GPVs) in cancer predisposition genes is increasingly offered as part of routine care for patients with cancer. This is often urgent in oncology clinics due to potential implications on treatment and surgical decisions. This also allows identification of family members who should be offered predictive genetic testing.
View Article and Find Full Text PDFArticle Synopsis
- Patient decision aids (PtDA) are tools that enhance shared decision-making between patients and healthcare professionals, aiming to improve the quality of decisions, particularly for those at increased genetic cancer risks.
- The workshop involved patients discussing their health decision-making priorities alongside psychological and behavioral theories to help shape a PtDA that resonates with their needs.
- Feedback revealed that decision-making is highly personal and context-dependent, indicating a flexible approach to the PtDA's design is necessary for better patient care and support.
"Switching the mind off completely" - Understanding the psychology of rest in coaches.
Psychol Sport Exerc
November 2023
Objectives: To better understand the psychology of rest in coaches. Rest appears to be important for coping, recovery, and well-being in coaches, yet there is limited research on and in turn understanding of this concept in this population.
Design: A qualitative description study design was employed.
While strategic self-talk interventions are well documented, less is known regarding organically occurring self-talk. Previously, eight organic self-talk content categories were identified, however contextual and personal factors relating to these categories is unexplored. The aim of the study was to explore the relationships between stress, coping, athletic identity, demographic and sport-related factors and the eight organic self-talk categories of anxiety control, confidence, disengagement, instruction, psych-up, somatic fatigue, worry, and irrelevant.
View Article and Find Full Text PDFArticle Synopsis
- Polygenic risk scores (PRSs), derived from genome-wide association studies (GWASs), can enhance breast cancer risk evaluation but are primarily based on European populations.
- This study analyzed the effectiveness of European-based PRS models in identifying breast cancer risk among Ashkenazi Jewish women in Israel using data from two cohorts.
- Results indicated that these PRS models successfully identified Ashkenazi Jewish women at high risk for breast cancer, suggesting they could improve risk assessment in this group.
Article Synopsis
- Breast cancer patients with the CHEK2 c.1100delC variant have a heightened risk of developing a second breast cancer (contralateral breast cancer) and generally experience worse survival outcomes compared to those without the variant.
- A study involving over 82,000 women aimed to evaluate how the CHEK2 variant, radiotherapy, and systemic treatments affect the risk of contralateral breast cancer and breast cancer-specific survival.
- Findings indicated that while systemic therapy (especially the combination of chemotherapy and endocrine therapy) lowers the risk of contralateral breast cancer, CHEK2 c.1100delC carriers still faced poorer survival rates, suggesting other factors at play beyond the risk of developing a second cancer.*
Article Synopsis
- Patients with genetic cancer susceptibility face challenging choices regarding testing, treatment, and risk management, leading to a need for effective decision support resources.
- A systematic review highlighted 36 studies on decision aids, revealing diverse resource types and mixed but generally positive effects on patients’ cognitive, emotional, and behavioral outcomes.
- There is a need for further research and development of tailored, patient-centered resources to improve decision-making and ensure successful follow-through on choices, particularly in oncology settings.
Background: Women with low-grade ovarian serous carcinoma (LGSC) benefit from surgical treatment; however, the role of chemotherapy is controversial. We examined an international database through the Ovarian Cancer Association Consortium to identify factors that affect survival in LGSC.
Methods: We performed a retrospective cohort analysis of patients with LGSC who had had primary surgery and had overall survival data available.
Objective: This study aimed to provide an up-to-date systematic review of "the long-term outcomes of bilateral salpingo-oophorectomy at the time of hysterectomy" and perform a meta-analysis for the reported associations.
Data Sources: Our study updated a previous systematic review by searching the literature using PubMed, Web of Science, and Embase for publications between January 2015 and August 2022.
Study Eligibility Criteria: Our study included studies of women who had a hysterectomy with bilateral salpingo-oophorectomy vs women who had a hysterectomy with ovarian conservation or no surgery.