Prostate Cancer Risk by BRCA2 Genomic Regions

A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3') wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a prospective cohort study of 447 male BRCA2 PV carriers recruited in the UK and Ireland from 1998 to 2016, we estimated standardised incidence ratios (SIRs) compared with population incidences and assessed variation in risk by PV location. Carriers of PVs in the PCCR had a PCa SIR of 8.33 (95% confidence interval [CI] 4.46-15.6) and were at a higher risk of PCa than carriers of other BRCA2 PVs (SIR = 3.31, 95% CI 1.97-5.57; hazard ratio = 2.34, 95% CI 1.09-5.03). PCCR PV carriers had an estimated cumulative PCa risk of 44% (95% CI 23-72%) by the age of 75 yr and 78% (95% CI 54-94%) by the age of 85 yr. Our results corroborate the existence of a PCCR in BRCA2 in a prospective cohort. PATIENT SUMMARY: In this report, we investigated whether the risk of prostate cancer for men with a harmful mutation in the BRCA2 gene differs based on where in the gene the mutation is located. We found that men with mutations in one region of BRCA2 had a higher risk of prostate cancer than men with mutations elsewhere in the gene.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This work was supported by Cancer Research UK grants C12292/A20861 and C12292/A22820. EMBRACE was supported by Cancer Research UK grantsC1287/A23382 and C1287/A26886. D. Gareth Evans is supported by a National Institute for Health Research grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). Rosalind Eeles is supported by Cancer Research UK grant C5047/A8385, and by National Institute for Health Research support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trustpublished version, accepted version (12 month embargo), submitted versio

A female perspective: Experiences of fashion, textiles, clothing and design

BACKGROUND: Carole Hunt (Art, Design, and Fashion) and Gayle Brewer (Psychology) at the University of Central Lancashire are currently investigating the extent to which female designers’ personal experiences impact on the design process of women’s clothing. The research is driven by theme rather than discipline, and focuses on a combination of clothing, textiles, visual appearance, gender and identity. Participants are final year Fashion Design students, who have had a year’s experience in industry. There are two key themes. 1. Body image, appearance and dissatisfaction are positioned within debates on subjectivity and identity, and are associated with a range of negative consequences including anxiety and depression. The fashion industry is said to have created a toxic environment that increases the likelihood of eating disorders. There is little research into the experience of those, other than models, who work in the fashion industry. 2. How do social, cultural and symbolic experiences of clothing, beauty and the body, affect design practice and the finished garment? METHOD: Participants complete a questionnaire identifying demographic status, professional training and experience of design. Semi-structured interviews are then conducted inviting participants to narrate and reflect on their experiences. Visual data is collected from participants’ studio work. How are designers’ social, cultural, and symbolic experiences of textiles, clothing and physical appearance conveyed and communicated through the fashion design visually, as well as through language? FINDINGS: Four distinct themes are emerging: 1. Differences between the University studio, and being “out there” in industry: being judged on appearance has had a negative impact on selfimage. 2. Social and cultural influences informing perceptions of women’s’ physical appearance. Students sought to challenge stereotypes through their design work. 3. A dichotomy between negative self-image and customer, described as in her twenties, strong, confident, financially independent; a woman unafraid to stand out. 4. Clothing as shelter, a protection from value judgements. Clothing as a ‘stylish fortress’ is a common theme. DISCUSSION: 1. Issues of health and well-being of fashion design students including physical appearance, disordered eating and weight related issues. 2. Social and cultural influences on gender identity. 3. Interdisciplinary and multidisciplinary research methods

Carole Brewer and Amelia Carter in a Junior Recital

This is the program for the junior recital of soprano, Amelia Carter, accompanied by pianist, Carolyn Yeldell, and junior piano recital of Carole Brewer. The recital was held on April 7, 1967

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Purpose: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. Methods: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10-50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10-12) carriers. The associations in the prospective cohort were similar. Conclusion: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.P20 GM130423/GM/NIGMS NIH HHS/United Statespublished version, accepted version (6 month embargo), submitted versio

Exposure to the Fashion Industry: A Design Student Perspective

It has been argued that the fashion industry represents a ‘toxic’ environment, which increases the incidence of body dissatisfaction and eating disorders amongst both fashion models and consumers [Treasure, J. L., Wack, E. R., & Roberts, M. R. (2008). Models as a high-risk group: The health implications of a size zero culture. The British Journal of Psychiatry, 192, 243–244]. There is,however, a paucity of information investigating the experiences of designers working in the fashion industry. The present study addresses this limitation and considers the experiences of female fashion design students. Interviews were conducted with eight students and subjected to interpretative phenomenological analysis. Three master themes emerged from the analysis. These were: Personal Style; Body Dissatisfaction; and Design. Two sub-themes formed the Personal Style theme: Casual and Comfortable and Covered and Protected. The Body Dissatisfaction theme contained two sub-themes: Personal Experience and Industry Exposure. The Design theme contained three sub-themes: Strength and Confidence; Differences Between Personal Style and Design; and Gender. Findings have important implications for the recruitment, retention, and well-being of female fashion design students

Технология и техника сооружения поисково-оценочных скважин на Майском месторождении алмазов (Республика Саха (Якутия))

Объектом исследования является кимберлитовая руда на объекте "Майское". Цель работы: составление проекта на бурение поисково-оценочных скважин; геологическое изучение объекта; разработка технологии проведе-ния поисковых работ на участке; разработка управления и организации работ на объекте. В процессе проектирования проводились: выбор бурового оборудования; поверочный расчет выбранного оборудования; расчет режимных параметров; анализ вредных и опасных факторов при проведении геологоразведочных работ и меры по их предупреждению; выбор вспомогательного оборудования и организации работ; сметно-финансовый расчет.The object of the study is kimberlite ore at the Mayskoye facility. The purpose of the work: preparation of the project for the drilling of exploration and evaluation wells; geological study of the object; development of technology for prospecting works on the site; development of management and organization of works on the site. In the process of design were carried out: selection of drilling equipment; calibration calculation of the selected equipment; calculation of operating parameters; analysis of harmful and dangerous factors during exploration and measures to prevent them; selection of auxiliary equipment and organization of wo

Risks of breast or ovarian cancer in BRCA1 or BRCA2 predictive test negatives: findings from the EMBRACE study.

Purpose BRCA1/BRCA2 predictive test negatives are proven noncarriers of a BRCA1/BRCA2 mutation that is carried by their relatives. The risk of developing breast cancer (BC) or epithelial ovarian cancer (EOC) in these women is uncertain. The study aimed to estimate risks of invasive BC and EOC in a large cohort of BRCA1/BRCA2 predictive test negatives. Methods We used cohort analysis to estimate incidences, cumulative risks, and standardized incidence ratios (SIRs). Results A total of 1,895 unaffected women were eligible for inclusion in the BC risk analysis and 1,736 in the EOC risk analysis. There were 23 incident invasive BCs and 2 EOCs. The cumulative risk of invasive BC was 9.4% (95% confidence interval (CI) 5.9-15%) by age 85 years and the corresponding risk of EOC was 0.6% (95% CI 0.2-2.6%). The SIR for invasive BC was 0.93 (95% CI 0.62-1.40) in the overall cohort, 0.85 (95% CI 0.48-1.50) in noncarriers from BRCA1 families, and 1.03 (95% CI 0.57-1.87) in noncarriers from BRCA2 families. The SIR for EOC was 0.79 (95% CI 0.20-3.17) in the overall cohort. Conclusion Our results did not provide evidence for elevated risks of invasive BC or EOC in BRCA1/BRCA2 predictive test negatives. Genetics in Medicine advance online publication, 22 March 2018; doi:10.1038/gim.2018.44

Prostate Cancer Risk by BRCA2 Genomic Regions.

A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3') wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a prospective cohort study of 447 male BRCA2 PV carriers recruited in the UK and Ireland from 1998 to 2016, we estimated standardised incidence ratios (SIRs) compared with population incidences and assessed variation in risk by PV location. Carriers of PVs in the PCCR had a PCa SIR of 8.33 (95% confidence interval [CI] 4.46-15.6) and were at a higher risk of PCa than carriers of other BRCA2 PVs (SIR = 3.31, 95% CI 1.97-5.57; hazard ratio = 2.34, 95% CI 1.09-5.03). PCCR PV carriers had an estimated cumulative PCa risk of 44% (95% CI 23-72%) by the age of 75 yr and 78% (95% CI 54-94%) by the age of 85 yr. Our results corroborate the existence of a PCCR in BRCA2 in a prospective cohort. PATIENT SUMMARY: In this report, we investigated whether the risk of prostate cancer for men with a harmful mutation in the BRCA2 gene differs based on where in the gene the mutation is located. We found that men with mutations in one region of BRCA2 had a higher risk of prostate cancer than men with mutations elsewhere in the gene

Prostate Cancer Risks for Male BRCA1 and BRCA2 Mutation Carriers: A Prospective Cohort Study.

BACKGROUND: BRCA1 and BRCA2 mutations have been associated with prostate cancer (PCa) risk but a wide range of risk estimates have been reported that are based on retrospective studies. OBJECTIVE: To estimate relative and absolute PCa risks associated with BRCA1/2 mutations and to assess risk modification by age, family history, and mutation location. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study of male BRCA1 (n = 376) and BRCA2 carriers (n = 447) identified in clinical genetics centres in the UK and Ireland (median follow-up 5.9 and 5.3 yr, respectively). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardised incidence/mortality ratios (SIRs/SMRs) relative to population incidences or mortality rates, absolute risks, and hazard ratios (HRs) were estimated using cohort and survival analysis methods. RESULTS AND LIMITATIONS: Sixteen BRCA1 and 26 BRCA2 carriers were diagnosed with PCa during follow-up. BRCA2 carriers had an SIR of 4.45 (95% confidence interval [CI] 2.99-6.61) and absolute PCa risk of 27% (95% CI 17-41%) and 60% (95% CI 43-78%) by ages 75 and 85 yr, respectively. For BRCA1 carriers, the overall SIR was 2.35 (95% CI 1.43-3.88); the corresponding SIR at age <65 yr was 3.57 (95% CI 1.68-7.58). However, the BRCA1 SIR varied between 0.74 and 2.83 in sensitivity analyses to assess potential screening effects. PCa risk for BRCA2 carriers increased with family history (HR per affected relative 1.68, 95% CI 0.99-2.85). BRCA2 mutations in the region bounded by positions c.2831 and c.6401 were associated with an SIR of 2.46 (95% CI 1.07-5.64) compared to population incidences, corresponding to lower PCa risk (HR 0.37, 95% CI 0.14-0.96) than for mutations outside the region. BRCA2 carriers had a stronger association with Gleason score ≥7 (SIR 5.07, 95% CI 3.20-8.02) than Gleason score ≤6 PCa (SIR 3.03, 95% CI 1.24-7.44), and a higher risk of death from PCa (SMR 3.85, 95% CI 1.44-10.3). Limitations include potential screening effects for these known mutation carriers; however, the BRCA2 results were robust to multiple sensitivity analyses. CONCLUSIONS: The results substantiate PCa risk patterns indicated by retrospective analyses for BRCA2 carriers, including further evidence of association with aggressive PCa, and give some support for a weaker association in BRCA1 carriers. PATIENT SUMMARY: In this study we followed unaffected men known to carry mutations in the BRCA1 and BRCA2 genes to investigate whether they are at higher risk of developing prostate cancer compared to the general population. We found that carriers of BRCA2 mutations have a high risk of developing prostate cancer, particularly more aggressive prostate cancer, and that this risk varies by family history of prostate cancer and the location of the mutation within the gene