Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Demographic and psychosocial features of participants in bondage and discipline, "sadomasochism" or dominance and submission (BDSM): data from a national survey

Introduction: People with sexual interests in bondage and discipline, “sadomasochism” or dominance and submission (BDSM) have been seen by many professionals as damaged or dangerous. Aim: To examine sexual behavior correlates of involvement in BDSM and test the hypothesis that BDSM is practiced by people with a history of sexual coercion, sexual difficulties, and/or psychological problems. Methods: In Australia in 2001–2002, a representative sample of 19,307 respondents aged 16–59 years was interviewed by telephone. Weighted data analysis used univariate logistic regression. Main Outcome Measures: Self-reported demographic and psychosocial factors; sexual behavior and identity; sexual difficulties. Results: In total, 1.8% of sexually active people (2.2% of men, 1.3% of women) said they had been involved in BDSM in the previous year. This was more common among gay/lesbian and bisexual people. People who had engaged in BDSM were more likely to have experienced oral sex and/or anal sex, to have had more than one partner in the past year, to have had sex with someone other than their regular partner, and to have: taken part in phone sex, visited an Internet sex site, viewed an X-rated (pornographic) film or video, used a sex toy, had group sex, or taken part in manual stimulation of the anus, fisting or rimming. However, they were no more likely to have been coerced into sexual activity, and were not significantly more likely to be unhappy or anxious—indeed, men who had engaged in BDSM scored significantly lower on a scale of psychological distress than other men. Engagement in BDSM was not significantly related to any sexual difficulties. Conclusion: Our findings support the idea that BDSM is simply a sexual interest or subculture attractive to a minority, and for most participants not a pathological symptom of past abuse or difficulty with “normal” sex

Factors affecting outcomes following pelvic exenteration for locally recurrent rectal cancer

Background: Pelvic exenteration for locally recurrent rectal cancer (LRRC) is associated with variable outcomes, with the majority of data from single-centre series. This study analysed data from an international collaboration to determine robust parameters that could inform clinical decision-making. Methods: Anonymized data on patients who had pelvic exenteration for LRRC between 2004 and 2014 were accrued from 27 specialist centres. The primary endpoint was survival. The impact of resection margin, bone resection, node status and use of neoadjuvant therapy (before exenteration) was assessed. Results: Of 1184 patients, 614 (51\ub79 per cent) had neoadjuvant therapy. A clear resection margin (R0 resection) was achieved in 55\ub74 per cent of operations. Twenty-one patients (1\ub78 per cent) died within 30 days and 380 (32\ub71 per cent) experienced a major complication. Median overall survival was 36 months following R0 resection, 27 months after R1 resection and 16 months following R2 resection (P < 0\ub7001). Patients who received neoadjuvant therapy had more postoperative complications (unadjusted odds ratio (OR) 1\ub753), readmissions (unadjusted OR 2\ub733) and radiological reinterventions (unadjusted OR 2\ub712). Three-year survival rates were 48\ub71 per cent, 33\ub79 per cent and 15 per cent respectively. Bone resection (when required) was associated with a longer median survival (36 versus 29 months; P < 0\ub7001). Node-positive patients had a shorter median overall survival than those with node-negative disease (22 versus 29 months respectively). Multivariable analysis identified margin status and bone resection as significant determinants of long-term survival. Conclusion: Negative margins and bone resection (where needed) were identified as the most important factors influencing overall survival. Neoadjuvant therapy before pelvic exenteration did not affect survival, but was associated with higher rates of readmission, complications and radiological reintervention