Deleterious germline mutations in BRIP1 are associated with a moderate increase in EOC risk. These data have clinical implications for risk prediction and prevention approaches for ovarian cancer and emphasize the critical need for risk estimates based on very large sample sizes before genes of moderate penetrance have clinical utility in cancer prevention.

Purpose The aim of this study was to estimate the contribution of deleterious mutations in the RAD51B, RAD51C, and RAD51D genes to invasive epithelial ovarian cancer (EOC) in the population and in a screening trial of individuals at high risk of ovarian cancer. Patients and Methods The coding sequence and splice site boundaries of the three RAD51 genes were sequenced and analyzed in germline DNA from a case-control study of 3,429 patients with invasive EOC and 2,772 controls as well as in 2,000 unaffected women who were BRCA1/BRCA2 negative from the United Kingdom Familial Ovarian Cancer Screening Study (UK_FOCSS) after quality-control analysis. Results In the case-control study, we identified predicted deleterious mutations in 28 EOC cases (0.82%) compared with three controls (0.11%; P < .001). Mutations in EOC cases were more frequent in RAD51C (14 occurrences, 0.41%) and RAD51D (12 occurrences, 0.35%) than in RAD51B (two occurrences, 0.06%). RAD51C mutations were associated with an odds ratio of 5.2 (95% CI, 1.1 to 24; P = .035), and RAD51D mutations conferred an odds ratio of 12 (95% CI, 1.5 to 90; P = .019). We identified 13 RAD51 mutations (0.65%) in unaffected UK_FOCSS participants (RAD51C, n = 7; RAD51D, n = 5; and RAD51B, n = 1), which was a significantly greater rate than in controls (P < .001); furthermore, RAD51 mutation carriers were more likely than noncarriers to have a family history of ovarian cancer (P < .001). Conclusion These results confirm that RAD51C and RAD51D are moderate ovarian cancer susceptibility genes and suggest that they confer levels of risk of EOC that may warrant their use alongside BRCA1 and BRCA2 in routine clinical genetic testing.

BackgroundGenetic testing for risk of hereditary cancer can help patients to make important decisions about prevention or early detection. US and UK studies show that people from ethnic minority groups are less likely to receive genetic testing. It is important to understand various groups’ awareness of genetic testing and its acceptability to avoid further disparities in health care. This review aims to identify and detail awareness, knowledge, perceptions, and attitudes towards genetic counselling/testing for cancer risk prediction in ethnic minority groups.MethodsA search was carried out in PsycInfo, CINAHL, Embase and MEDLINE. Search terms referred to ethnicity, genetic testing/counselling, cancer, awareness, knowledge, attitudes, and perceptions. Quantitative and qualitative studies, written in English, and published between 2000 and 2015, were included.ResultsForty-one studies were selected for review: 39 from the US, and two from Australia. Results revealed low awareness and knowledge of genetic counselling/testing for cancer susceptibility amongst ethnic minority groups including African Americans, Asian Americans, and Hispanics. Attitudes towards genetic testing were generally positive; perceived benefits included positive implications for personal health and being able to inform family. However, negative attitudes were also evident, particularly the anticipated emotional impact of test results, and concerns about confidentiality, stigma, and discrimination. Chinese Australian groups were less studied, but of interest was a finding from qualitative research indicating that different views of who close family members are could impact on reported family history of cancer, which could in turn impact a risk assessment.ConclusionInterventions are needed to increase awareness and knowledge of genetic testing for cancer risk and to reduce the perceived stigma and taboo surrounding the topic of cancer in ethnic minority groups. More detailed research is needed in countries other than the US and across a broader spectrum of ethnic minority groups to develop effective culturally sensitive approaches for cancer prevention.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-017-4375-8) contains supplementary material, which is available to authorized users.

PurposeTo establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC).Patients and MethodsWomen whose estimated lifetime risk of OC/FTC was ≥ 10% were recruited at 42 centers in the United Kingdom and underwent ROCA screening every 4 months. TVS occurred annually if ROCA results were normal or within 2 months of an abnormal ROCA result. Risk-reducing salpingo-oophorectomy (RRSO) was encouraged throughout the study. Participants were observed via cancer registries, questionnaires, and notification by centers. Performance was calculated after censoring 365 days after prior screen, with modeling of occult cancers detected at RRSO.ResultsBetween June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients were diagnosed with invasive OC/FTC within 1 year of prior screening (13 diagnoses were screen-detected and six were occult at RRSO). No symptomatic interval cancers occurred. Ten (52.6%) of the total 19 diagnoses were stage I to II OC/FTC (CI, 28.9% to 75.6%). Of the 13 screen-detected cancers, five (38.5%) were stage I to II (CI, 13.9% to 68.4%). Of the six occult cancers, five (83.3%) were stage I to II (CI, 35.9% to 99.6%). Modeled sensitivity, positive predictive value, and negative predictive value for OC/FTC detection within 1 year were 94.7% (CI, 74.0% to 99.9%), 10.8% (6.5% to 16.5%), and 100% (CI, 100% to 100%), respectively. Seven (36.8%) of the 19 cancers diagnosed < 1 year after prior screen were stage IIIb to IV (CI, 16.3% to 61.6%) compared with 17 (94.4%) of 18 cancers diagnosed > 1 year after screening ended (CI, 72.7% to 99.9%; P < .001). Eighteen (94.8%) of 19 cancers diagnosed < 1 year after prior screen had zero residual disease (with lower surgical complexity, P = .16) (CI, 74.0% to 99.9%) compared with 13 (72.2%) of 18 cancers subsequently diagnosed (CI, 46.5% to 90.3%; P = .09).ConclusionROCA-based screening is an option for women at high risk of OC/FTC who defer or decline RRSO, given its high sensitivity and significant stage shift. However, it remains unknown whether this strategy would improve survival in screened high-risk women.

The majority of BRCA gene mutation carriers are supportive of offering PGD to others, thus endorsing the HFEA decision. However, most women would not consider it personally. Concerns raised highlight the need for regular HFEA reviews of the licensing criteria, as HBOC may cease to be a "serious life threatening illness" in the future.

A B S T R A C T PurposeTo establish the performance characteristics of annual transvaginal ultrasound and serum CA125 screening for women at high risk of ovarian/fallopian tube cancer (OC/FTC) and to investigate the impact of delayed screening interval and surgical intervention. Between May 6, 2002, and January 5, 2008, 3,563 women at an estimated Ն 10% lifetime risk of OC/FTC were recruited and screened by 37 centers in the United Kingdom. Participants were observed prospectively by centers, questionnaire, and national cancer registries. Patients and Methods ResultsSensitivity for detection of incident OC/FTC at 1 year after last annual screen was 81.3% (95% CI, 54.3% to 96.0%) if occult cancers were classified as false negatives and 87.5% (95% CI, 61.7% to 98.5%) if they were classified as true positives. Positive and negative predictive values of incident screening were 25.5% (95% CI, 14.3 to 40.0) and 99.9% (95% CI, 99.8 to 100) respectively. Four (30.8%) of 13 incident screen-detected OC/FTCs were stage I or II. Compared with women screened in the year before diagnosis, those not screened in the year before diagnosis were more likely to have Ն stage IIIc disease (85.7% v 26.1%; P ϭ .009). Screening interval was delayed by a median of 88 days before detection of incident OC/FTC. Median interval from detection screen to surgical intervention was 79 days in prevalent and incident OC/FTC. ConclusionThese results in the high-risk population highlight the need for strict adherence to screening schedule. Screening more frequently than annually with prompt surgical intervention seems to offer a better chance of early-stage detection.

Interference in attending to emotionally salient stimuli appears to be related to measures of anxiety and depression rather than pain per se. When added to the findings of other investigators, these results suggest that the presence of attentional biases in chronic pain patients can best be accounted for as arising from mood state rather than pain-patient status.

Prevalence, frequency and problem rating of hot flushes persist in older postmenopausal women: impact of age, body mass index, hysterectomy, hormone therapy use, lifestyle and mood in a cross-sectional cohort study of 10 418 British women aged 54-65 Objective Hot flushes and night sweats (HFs/NSs) are the main menopausal symptoms, but few studies have been adequately powered to examine the dimensions or predictors of experiencing HFs/NSs. We report on these variables in a large UK cohort of postmenopausal women.Design Cross-sectional cohort study.Setting UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) cohort. Methods Women completed a follow-up questionnaire, and those aged 54-65 years were mailed a survey in July 2008.Main outcome measures Hot flush prevalence and hot flush rating scale.Results Of the 15 000 women mailed, 10 418 returned completed questionnaires; 90% had previously had HFs/NSs. Despite being on average 10 years postmenopausal, 54% experienced HFs/NSs (frequency of 33 per week with mean problem rating 4/10) that persisted across the age range. Past hysterectomy (OR 1.50, 95% CI 1.19-1.86), ever having smoked (OR 1.27, 95% CI 1.11-1.46) and alcohol consumption (current units) (OR 1.05, 95% CI 1.01-1.09) predicted ever having had HFs/NSs. Anxiety (OR 3.09, 95% CI 2.57-3.72), hysterectomy (OR 2.74, 95% CI 2.32-3.25), depressed mood (OR 1.57, 95% CI 1.24-1.99), years since last menstrual period (OR 0.95, 95% CI 0.94-0.96) and education (above and below 18 years) (OR 0.98, 95% CI 0.97-0.99) predicted the current prevalence of HFs/NSs. Few predictors of frequency were identified, but problem rating was associated with depressed mood, hysterectomy, skirt size increase and frequency of HFs/NSs. Past hormone therapy users who had discontinued treatment were more likely to have HFs/NSs that were more frequent and problematic.Conclusions To date, this is the largest UK study of the experience of HFs/NSs amongst older postmenopausal women. HFs/NSs are more prevalent in this age band than has previously been assumed. These findings and the associations of smoking, hysterectomy, anxiety, depressed mood and hormone therapy use with the experience of HFs/NSs have implications for prevention and symptom management.