Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry.

BACKGROUND: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. METHODS: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. RESULTS: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10-6) and AC058822.1 (P = 1.47 × 10-4), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. CONCLUSIONS: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10-5), demonstrating the importance of diversifying study cohorts

Adapting an evidence-based HIV behavioral intervention for South African couples

Background: In South Africa, heterosexual couples are at risk for HIV infection and transmission through substance use, gender-based violence and traditional gender roles, and sex risk behaviors such as having multiple partners and unsafe sex. Methods: To address these interconnected HIV risks among heterosexual couples, we used the ADAPT framework to modify an existing, efficacious women's HIV prevention intervention (the Western Cape Women's Health CoOp) to include components of an evidence-based couple's intervention from the United States (Project Connect) and components from the Men as Partners program that has been used successfully in South Africa. We conducted focus groups with men, women and couples, and obtained feedback from a long-standing Community Collaborative Board (CCB) to guide the synthesis of elements of these three interventions into a new intervention. We then piloted the adapted intervention for feasibility and acceptability. Results: The new intervention is called the Couples' Health CoOp. This intervention targets men who use alcohol and other drugs and engage in unprotected sex, and their main female sex partners. The intervention addresses substance use, sex risk, HIV and other sexually transmitted infections, gender roles, gender-based violence, communication skills, and goal-setting activities to increase sexy (eroticize) safe-sex behaviors. The Couples' Health CoOp also includes "voices" from the focus group members to ground the intervention in the experiences of these at-risk couples. In addition, it utilizes a participant handbook that reiterates workshop content and includes homework assignments for couples to complete together to increase problem-solving skills within their relationship, and to improve their sexual relationship and help sustain HIV risk-reduction strategies. All of these adaptations were based on participants' suggestions made during formative work and pilot testing. Conclusions: The Couples' Health CoOp is a couple-based HIV prevention intervention that targets alcohol and other drug use to reduce sexual risk, reduce gender-based violence and offer alternatives for conflict resolution, promote healthy relationships, and modify traditional gender roles in South Africa

Barriers and facilitators to implementing an evidence-based woman-focused intervention in South African health services

Background: Since the beginning of the HIV epidemic, numerous behavior change, risk-reduction, and biomedical interventions have been developed and tested. While some of these interventions have shown to be efficacious in randomized trials, it often takes almost two decades for an intervention to be translated into practice. Meanwhile, South Africa continues to have among the highest prevalence of HIV globally, with women of childbearing age bearing the burden of the epidemic. Given the urgency of the HIV epidemic among vulnerable women in South Africa, it is imperative that evidence-based interventions be implemented rapidly into practice. This study presents a first step toward examining the acceptability and feasibility of implementing the Women's Health CoOp (WHC) in clinics and substance abuse rehab settings in Cape Town, South Africa. Methods: We conducted focus group discussions with women who use substances and with service providers, we also conducted in-depth interviews with health service planners. Our goal was to examine implementation and clinical outcomes associated with delivery of the WHC across clinics and substance abuse rehab programs. Results: All participants agreed on the need for the WHC. Perceived facilitators to implementing the WHC included the recognizable need for programs to empower women and to build the capacity of staff to address issues of substance use, sexual risk, and intimate partner violence. Participants also identified potential barriers to women engaging with this program, including the stigma women experience when seeking services and the lack of person-centered care at healthcare facilities. Conclusions: In a country with the largest number of women of childbearing age living with HIV, an evidence-based woman-focused intervention that comprehensively addresses women's risk for suboptimal antiretroviral adherence may be essential for reducing HIV incidence. However, potential barriers to implementing the WHC successfully must be addressed before the program can be fully integrated into the services delivered by healthcare facilities. Trial registration: Clinical trials NCT02733003. Date of Registration: January 21, 2016, registered retroactively after participant enrollment

Aggressive behaviour among drug-using women from Cape Town, South Africa: Ethnicity, heavy alcohol use, methamphetamine and intimate partner violence

Background: Women have generally been found to be the victims of violence, but scant attention has been paid to the characteristics of women who perpetrate aggression and violence. In South Africa, violence is a prevalent societal issue, especially in the Western Cape. Method: This study aimed at identifying factors that were associated with aggression among a sample of 720 substance-using women. We conducted multivariate logistic regression to identify factors that are significantly associated with these behaviours. Results: Ethnicity (Wald X2 = 17.07(2), p < 0.01) and heavy drinking (Wald X2 = 6.60 (2), p = 0.01) were significantly related to verbal aggression, methamphetamine use was significantly related to physical (Wald X2 = 2.73 (2), p = 0.01) and weapon aggression (Wald X2 = 7.94 (2), p < 0.01) and intimate partner violence was significantly related to verbal (Wald X2 = 12.43 (2), p < 0.01) and physical aggression (Wald X2 = 25.92 (2), p < 0.01). Conclusions: The findings show high levels of aggression among this sample, and highlight the need for interventions that address methamphetamine, heavy drinking and intimate partner violence among vulnerable substance-using women