"Should I Let Them Know I Have This?": Multifaceted Genetic Discrimination and Limited Awareness of Legal Protections among Individuals with Hereditary Cancer Syndromes.

Introduction: Hereditary cancer syndromes (HCS), such as hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome (LS), represent approximately 10% of all cancers. Along with medical burdens associated with the genetic risk of developing cancer, many individuals face stigma and discrimination. Genetic discrimination refers to negative treatment, unfair profiling, or harm based on genetic characteristics, manifesting as "felt" stigma (ostracization without discriminatory acts) or "enacted" stigma (experiencing discriminatory acts).

Economic Evaluation of Population-Based BRCA1 and BRCA2 Testing in Canada.

Importance: Population-based BRCA testing can identify many more BRCA carriers who will be missed by the current practice of BRCA testing based on family history (FH) and clinical criteria. These carriers can benefit from screening and prevention, potentially preventing many more breast and ovarian cancers and deaths than the current practice.

Objective: To estimate the incremental lifetime health outcomes, costs, and cost-effectiveness associated with population-based BRCA testing compared with FH-based testing in Canada.

Exploring family communication preferences in hereditary breast and ovarian cancer and Lynch syndrome: a national Canadian survey.

Background: Individuals affected with cancer predisposition (CPS) syndromes such as BRCA1, BRCA2 or Lynch syndrome (LS) are at an elevated risk of multiple cancers. Identifying high-risk individuals is important if they are to access risk-reducing strategies. Interventions such as risk-reducing salpingo-oophorectomy in carriers of BRCA pathogenic or likely pathogenic (P/LP) variants or regular colonoscopy for carriers of LS P/LP variants are highly effective and reduce mortality.

"I just wanted more": Hereditary cancer syndromes patients' perspectives on the utility of circulating tumour DNA testing for cancer screening.

Hereditary cancer syndromes (HCS) predispose individuals to a higher risk of developing multiple cancers. However, current screening strategies have limited ability to screen for all cancer risks. Circulating tumour DNA (ctDNA) detects DNA fragments shed by tumour cells in the bloodstream and can potentially detect cancers early.

Gynecologic Cancer Risk and Genetics: Informing an Ideal Model of Gynecologic Cancer Prevention.

Individuals with proven hereditary cancer syndrome (HCS) such as and have elevated rates of ovarian, breast, and other cancers. If these high-risk people can be identified before a cancer is diagnosed, risk-reducing interventions are highly effective and can be lifesaving. Despite this evidence, the vast majority of Canadians with HCS are unaware of their risk.

Understanding the Experience of Canadian Women Living with Ovarian Cancer through the Every Woman Study.

The Every Woman StudyTM: Canadian Edition is the most comprehensive study to date exploring patient-reported experiences of ovarian cancer (OC) on a national scale. An online survey conducted in Fall 2020 included individuals diagnosed with OC in Canada, reporting responses from 557 women from 11 Canadian provinces/territories. Median age at diagnosis was 54 (11−80), 61% were diagnosed between 2016−2020, 59% were stage III/IV and all subtypes of OC were represented.

Bone health after RRBSO among mutation carriers: a population-based study.

Objective: Examine the risks of fractures and osteoporosis after risk-reducing bilateral salpingo-oophorectomy (RRBSO) among women with mutations.

Methods: In this retrospective population-based study in British Columbia, Canada, between 1996 to 2017, we compared risks of osteoporosis and fractures among women with mutations who underwent RRBSO before the age of 50 (n=329) with two age-matched groups without known mutations: 1) women who underwent bilateral oophorectomy (BO) (n=3,290); 2) women with intact ovaries who had hysterectomy or salpingectomy (n=3,290). Secondary outcomes were: having dual-energy X-ray absorptiometry (DEXA) scan, and bisphosphonates use.

"Game Changer": Health Professionals' Views on the Clinical Utility of Circulating Tumor DNA Testing in Hereditary Cancer Syndrome Management.

Background: We explored health professionals' views on the utility of circulating tumor DNA (ctDNA) testing in hereditary cancer syndrome (HCS) management.

Materials And Methods: A qualitative interpretive description study was conducted, using semi-structured interviews with professionals across Canada. Thematic analysis employing constant comparison was used for analysis.

Risk of cardiovascular disease among women carrying BRCA mutations after risk-reducing bilateral salpingo-oophorectomy: A population-based study.

Objective: Examine the risk of cardiovascular disease (CVD) following risk reducing bilateral salpingo-oophorectomy (RRBSO) among women with BRCA mutations.

Methods: In this retrospective population-based study in British Columbia, Canada, between 1996 and 2017, we compared the risk of CVD among women with known BRCA mutations who underwent RRBSO before the age of 50 (n = 360) with two groups of age-matched women without known BRCA mutations: 1) women who underwent bilateral oophorectomy (BO) for benign conditions (n = 3600); and, 2) women with intact ovaries who had hysterectomy or salpingectomy (n = 3600). Our primary outcome was CVD (a composite (any of) myocardial infarction, heart failure, and/or cerebrovascular disease).

Universal tumor screening for lynch syndrome: perspectives of patients regarding willingness and informed consent.

Lynch Syndrome is associated with a significant risk of colorectal carcinoma (CRC) and other cancers. Universal tumor screening is a strategy to identify high-risk individuals by testing all CRC tumors for molecular features suggestive of Lynch Syndrome. Patient interest in screening and preferences for consent have been underexplored.

Group plus "mini" individual pre-test genetic counselling sessions for hereditary cancer shorten provider time and improve patient satisfaction.

Background: Genetic counselling (GC) is an integral component in the care of individuals at risk for hereditary cancer predisposition syndromes (CPS). In many jurisdictions, access to timely counselling and testing is limited by financial constraints, by the shortage of genetics professionals and by labor-intensive traditional models of individual pre and post-test counselling. There is a need for further research regarding alternate methods of GC service delivery and implementation.

A dominant RAD51C pathogenic splicing variant predisposes to breast and ovarian cancer in the Newfoundland population due to founder effect.

Background: RAD51C is important in DNA repair and individuals with pathogenic RAD51C variants have increased risk of hereditary breast and ovarian cancer syndrome (HBOC), an autosomal dominant genetic predisposition to early onset breast and/or ovarian cancer.

Methods: Five female HBOC probands sequenced negative for moderate- and high-risk genes but shared a recurrent variant of uncertain significance in RAD51C (NM_058216.3: c.

Quality of life following prophylactic gynecological surgery: experiences of female Lynch mutation carriers.

Lynch syndrome (LS) is a genetic condition conferring an elevated risk of gastrointestinal, gynecologic and other malignancies, often before the age of 50. Current guidelines recommend prophylactic gynecologic surgery to manage inherited cancers for female mutation carriers. Data is lacking on women's quality of life following surgery.

Effect of vaginal self-sampling on cervical cancer screening rates: a community-based study in Newfoundland.

Background: Cervical cancer is highly preventable and treatable if detected early through regular screening. Women in the Canadian province of Newfoundland & Labrador have relatively low rates of cervical cancer screening, with rates of around 40 % between 2007 and 2009. Persistent infection with oncogenic human papillomavirus (HPV) is a necessary cause for the development of cervical cancer, and HPV testing, including self-sampling, has been suggested as an alternative method of cervical cancer screening that may alleviate some barriers to screening.

Decisions about prophylactic gynecologic surgery: a qualitative study of the experience of female Lynch syndrome mutation carriers.

Background: Women who carry a mutation for Lynch syndrome face complex decisions regarding strategies for managing their increased cancer risks. At present, there is limited understanding of the factors influencing women's prophylactic surgery decisions.

Methods: As part of an exploratory pilot project, semi-structured interviews were conducted with 10 women who were Lynch syndrome mutation carriers and had made prophylactic surgery decisions.

Randomized trial of oral misoprostol before endometrial biopsy.

Objective: To determine if the use of oral misoprostol in women undergoing endometrial biopsy reduces procedural discomfort.

Methods: Women undergoing endometrial biopsy were randomized to receive either 400 microg misoprostol or a vitamin B6 placebo orally 12 hours prior to the procedure, and were stratified based on menopausal status. The primary outcome was procedural discomfort on a visual analogue scale (0-10).

Human kallikrein related peptidases 6 and 13 in combination withCA125 is a more sensitive test for ovarian cancer than CA125 alone.

The current biomarker for ovarian cancer, CA125, lacks the sensitivity and specificity required to detect early stage ovarian cancers. Since several Kallikreins (KLKs) are up regulated in ovarian cancer, they represent a potential pool of biomarkers for ovarian cancer. The purpose of this study is to determine if elevated expression levels of Muc16 (CA125 gene), KLK6 and KLK13 represent a more sensitive test for detection of early stage ovarian cancer than Muc16 alone.

Update on granulosa cell tumours of the ovary.

Purpose Of Review: Granulosa cell tumours of the ovary are an uncommon ovarian sex-cord stromal tumour. These neoplasms provide a spectrum of clinical presentations that span from the first to the tenth decade. Surgery represents the primary therapy for early stage disease; however, management of women with advanced disease is less clear.

Familial risk of preeclampsia in Newfoundland: a population-based study.

This study sought to quantify the familial risk of preeclampsia (proteinuric hypertension) in Newfoundland and to identify characteristics in probands that predict increased familial risk. Reviewed were 5173 obstetric charts from 10 hospitals, representing 99% of deliveries on the island of Newfoundland for a 1-yr period from April 1996 to March 1997; pregnancy-induced hypertension was diagnosed according to strict criteria. Family obstetric histories were obtained from identified probands with preeclampsia, and sisters and mothers of probands were interviewed.