RESUMO
BACKGROUND: Increased risk of venous thromboembolism (VTE) is a life-threatening side effect for users of oral contraceptives (OCs) or hormone therapy (HT). OBJECTIVES: To investigate the potential for genetic predisposition to VTE in OC or HT users, we conducted a gene-by-environment case-only meta-analysis of genome-wide association studies (GWAS). METHODS: Use or nonuse of OCs (7 studies) or HT (8 studies) at the time of the VTE event was determined by pharmacy records or self-report. A synergy index (SI) was modeled for each variant in each study and submultiplicative/supramultiplicative gene-by-environment interactions were estimated. The SI parameters were first meta-analyzed across OC and HT studies and subsequently meta-analyzed to obtain an overall estimate. The primary analysis was agnostic GWAS and interrogated all imputed genotypes using a P value threshold of <5.0 × 10-8; secondary analyses were candidate-based. RESULTS: The VTE case-only OC meta-analysis included 2895 OC users and 6607 nonusers; the case-only HT meta-analysis included 2434 HT users and 12 793 nonusers. In primary GWAS meta-analyses, no variant reached genome-wide significance, but the smallest P value approached statistical significance: rs9386463 (P = 5.03 × 10-8). We tested associations for 138 candidate variants and identified 2 that exceeded statistical significance (0.05/138 = 3.62 × 10-4): F5 rs6025 (P = 1.87 × 10-5; SI, 1.29; previously observed) and F11 rs2036914 (P = 2.0 × 10-4; SI, 0.91; new observation). CONCLUSION: The candidate variant approach to identify submultiplictive/supramultiplicative associations between genetic variation and OC and HT use identified a new association with common genetic variation in F11, while the agnostic interrogations did not yield new discoveries.
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/genética , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/induzido quimicamente , Feminino , Fatores de Risco , Adulto , Interação Gene-Ambiente , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Medição de Risco , Anticoncepcionais Orais Hormonais/efeitos adversos , Anticoncepcionais Orais Hormonais/administração & dosagem , Variação Genética , Terapia de Reposição de Estrogênios/efeitos adversosRESUMO
Stress is a common belief among breast cancer patients and the public to explain variation in breast cancer incidence. Epidemiological studies interrogating the relationship between stress and cancer have reported mixed results. The impact of the topic and the lack of consensus has sparked this review of the literature to investigate gaps in knowledge and identify areas of research. We first present a brief summary of the biopsychosocial model generally used to conduct research on stress. We then divide the overview of the literature into areas of research focus. These include the role of distressing life events in breast cancer incidence, the role of adverse childhood events in later breast cancer incidence, the importance of race and socioeconomic status (SES) as social determinants of breast cancer incidence, and the specific role of chronic stress in relation to breast cancer. For each topic, we discuss the potential of stress as a risk factor and possible intervention strategies that could reduce the effects of stress. We then identify further research questions to be probed to fill the gaps in knowledge. We conclude with a discussion of future research directions for stress research as it relates to breast cancer incidence.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/epidemiologia , Criança , Humanos , Incidência , Fatores de Risco , Classe SocialRESUMO
Identifying patients with high genetic risk for cancer has important clinical ramifications, but hereditary cancer risk is often not identified because of testing barriers at both the provider and patient level. It is unknown how to best implement appropriate genetic testing and follow-up care into an operating primary care clinic. Implementation studies to date have been conducted in high resourced facilities under optimal conditions, often not at the clinic level. This study aims to compare and evaluate two population-wide engagement strategies for identifying members of a primary care clinic's population with a family or personal history of cancer and offering high-risk individuals genetic testing for cancer susceptibility mutations. The two engagement strategies are: 1) point of care screening (POC), conducted when a patient is scheduled for an appointment and 2) direct patient engagement (DPE), where outreach provides the patient an opportunity to complete screening online on their own time. The study will identify changes, problems, and inefficiencies in clinical flow during and after the implementation of risk assessment and genomic testing for cancer risk across primary care clinics. It will also evaluate the effects of the two engagement strategies on patient, provider, and clinic leader outcomes, including perceptions of benefits, harms, and satisfaction with the engagement strategy and process of cancer risk assessment and genetic testing, across gender, racial/ethnic, socioeconomic, and genetic literacy divides. Finally, the study will evaluate the cost-effectiveness and budget impact of each engagement strategy.