Public Health Genomics最新文献

Introduction: Given that PD-L1 is a crucial immune checkpoint in regulating T-cell responses, the aim of this study was to explore the impact of PD-L1 gene polymorphisms and the interaction with cooking with solid fuel on susceptibility to tuberculosis (TB) in Chinese Han populations.

Methods: A total of 503 TB patients and 494 healthy controls were enrolled in this case-control study. Mass spectrometry technology was applied to genotype rs2297136 and rs4143815 of PD-L1 genes. The associations between single nucleotide polymorphism (SNPs) and TB were assessed using unconditional logistic regression analysis. Marginal structural linear odds models were used to estimate the gene-environment interactions.

Results: Compared with genotype CC, genotypes GG and CG+GG at rs4143815 locus were significantly associated with susceptibility to TB (OR: 3.074 and 1.506, respectively, p < 0.05). However, no statistical association was found between rs2297136 SNP and TB risk. Moreover, the relative excess risk of interaction between rs4143815 of the PD-L1 gene and cooking with solid fuel was 2.365 (95% CI: 1.922-2.809), suggesting positive interactions with TB susceptibility.

Conclusion: The rs4143815 polymorphism of the PD-L1 gene was associated with susceptibility to TB in Chinese Han populations. There were significantly positive interactions between rs4143815 and cooking with solid fuel.

Introduction: The Generation Study (GS) aims to recruit 100,000 newborns in England to evaluate the utility and feasibility of using whole genome sequencing to screen for rare conditions that can be treated in early childhood; enable wider research to support further discovery in genomics and health; and explore the potential of storing an individual's genome over their lifetime. The GS incorporates complexities of consent in newborn screening, genomic medicine, and healthcare research, and there is a gap in exploring how to implement existing recommendations. Participant involvement has been shown to improve the implementation of processes and materials in healthcare. This paper describes how the GS team leveraged this through Design Research (DR) methodologies to develop the GS consent experience.

Methods: Over a 2-year period, 9 rounds of DR were undertaken with expectant and recent parents and a chosen partner (n = 105). Each round consisted of semi-structured interviews and a range of co-design and usability testing activities.

Results: DR activities highlighted areas for consideration for consent materials and processes. We describe common barriers and enablers across three stages of consent: awareness, consideration, and making an informed decision. As well as ensuring participants fully understand pros and cons of taking part, materials should consider pre-existing assumptions or misconceptions which may discourage parents from learning about the GS.

Conclusion: Involving parents in co-creation has broadened the perspective of what constitutes informed decision-making for newborn genome sequencing. Iterative rounds of research and design can provide tangible paths forward, supporting the successful implementation of informed decision-making.

Introduction: As the utility of genomic sequencing increases, its use in healthcare will continue to expand beyond expert clinics toward nonspecialist practices such as primary care. At the same time, discordance in genetic variant identification and classification between laboratories remains a concern for the field. This research assesses how clinicians with and without genetics expertise understand and trust genetic test results, underscoring how variation in the handling of genetic test results can have real impact on patient care.

Methods: We conducted 40 interviews with genetics experts, including clinical geneticists and genetic counselors, and nonexpert clinicians including primary care providers and cardiologists.

Results: Clinical geneticists and genetic counselors reported spending significant time assessing the validity of results from genetic testing laboratories, conversing with laboratories about those results, and potentially reinterpreting results. Conversely, primary care providers and cardiologists without specific genetics expertise reported high levels of trust in laboratory accuracy and variant interpretation, and did not reassess results.

Conclusion: We find significant variation in how genetics experts and nonexperts understand the trustworthiness of genetic laboratory reports. This variation could lead to differences in patient care between clinical settings and requires additional guidance for clinicians regarding the handling of genetic test results.

Introduction: Despite growing calls for the explicit application of theory when designing behaviour change interventions, limited empirical evidence exists regarding the effectiveness of these methods compared to non-theoretical approaches. A cluster randomized controlled trial (Hide and Seek Project - HaSP) tested two implementation approaches for improving hereditary cancer referral practices with one key distinction: implementation strategies were designed based explicitly on psychological theory or based on stakeholder intuition. This study presents the detailed methods and resources used to facilitate this comparison, whilst examining the strategies generated through both approaches.

Methods: Across seven Australian hospitals, clinical stakeholders attended focus groups to co-design site-specific strategies for improving Lynch syndrome referral. Co-design methods differed according to trial arm. Implementation strategy content was examined, with intuitively derived strategies retrospectively coded to determine theoretical alignment.

Results: Fifty-one strategies were proposed across all sites (theory-based arm = 32, intuition-based arm = 19). Overall, nine behaviour change technique (BCT) categories were used on 77 occasions. In the theory-based trial arm, eight BCT categories were identified on 53 occasions; and five BCT categories on 24 occasions in the intuition-based arm. BCT categories were largely similar across both arms. After retrospectively coding intuitively derived strategies, 42% contained mechanistic links, thereby demonstrating theoretical alignment.

Conclusion: Methods facilitated robust comparison of theoretical and intuitive approaches to implementation strategy design. Recognizing the known benefits of theory for enhancing scientific learning, applying these methods on a larger scale may provide definitive evidence about the comparative effectiveness of theoretical approaches.

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). This study aimed to describe concerns and experiences of genetic discrimination faced by individuals with HCS.

Methods: Semi-structured qualitative interviews were conducted with individuals with molecularly confirmed HCS residing in Ontario, British Columbia, and Newfoundland and Labrador, Canada. Purposive sampling was applied to obtain a diverse sample across demographic characteristics. Study procedures were informed by interpretive description; data were thematically analyzed using constant comparison.

Results: Seventy-three participants were interviewed (39 HBOC, 34 LS; 51 females, 21 males, 1 gender-diverse; aged 25-80). Participants described multifaceted forms of genetic discrimination across healthcare, insurance, employment, and family/social settings. Participants valued the Genetic Nondiscrimination Act's protective intent but demonstrated limited knowledge of its existence and provisions. Limited knowledge, coupled with policy constraints in non-legislative settings and third-party use of proxy genetic information, hindered participants' ability to whistleblow or seek recourse.

Conclusion: Our results illuminate a disconnection between the intended protective effects of genetic nondiscrimination legislation and ongoing genetic discrimination faced by individuals with hereditary conditions. To better support these individuals, this study encourages public outreach and knowledge translation efforts to increase awareness of nondiscrimination legal protections.

Introduction: In the USA, patients who undergo genetic testing for hereditary cancer risk are responsible for informing relatives about their genetic test results, but many relatives never find out they might be at risk. A health system-mediated relative notification program might help fill this gap, but questions remain about the acceptability of this approach.

Methods: We analyzed qualitative data from a single-arm, nonrandomized, mixed-methods study to understand how patients and families experienced a new health system-mediated relative notification program. We invited all study participants to participate in semi-structured telephone interviews at 6-8 weeks after return of genetic test results. We used a template analysis approach to thematically analyze interview transcripts.

Results: We interviewed 32 participants, including 17 probands and 15 relatives. Relatives reported positive experiences with the notification program, noting they felt in control of decisions and appreciated genetic counselor involvement in communicating the proband's test results. Benefits of direct contact included reduced burden for probands, increased family discussions about health, and notification of relatives who otherwise would not have learned results. No participants reported adverse effects from the program.

Conclusion: Overall, the relative notification program was acceptable to participants and supported probands in reaching at-risk relatives who otherwise might not have been notified. These findings could inform the implementation of future genetic risk family notification programs with the potential to improve uptake of cascade testing and advance cancer prevention and early detection efforts.

Introduction: Less than half of eligible Black women are assessed for genetic risk and only 28% engage in recommended hereditary breast and ovarian cancer (HBOC) risk-reducing interventions. CHWs are trusted individuals that work as a liaison between health systems and the community to improve access to services and support cancer prevention efforts, though they are an overlooked resource to support genetic risk assessment. To address the need and training gaps for CHWs, we developed and assessed an online training program to build CHW's competencies in cancer genomics and use of health information technologies to navigate high-risk individuals to appropriate genetic services.

Methods: The curriculum and 10 training modules were developed through engaging a panel of experts in a three-round Delphi process. Recruitment focused on CHWs who worked in clinical settings or groups providing outreach or health services to Black women. We assessed: changes in knowledge and attitudes about HBOC and genomics, as well as the perceptions about the quality and implementation of the training.

Results: Forty-six individuals expressed interest in the training after recruitment. Thirty eight individuals were eligible for the training and 26 completed the course. We found improvements in knowledge and genomics competencies immediately post-course, but the majority of these improvements were not sustained at 3-month follow-up. The training was highly rated for its relevance to CHW work and overall delivery. Top rated sessions included HBOC overview and family history collection. On average, participants reported discussing HBOC with 17 individuals at 3-month follow-up.

Conclusion: Championing a diverse cancer and genomics workforce can help address the goals of the National Cancer Plan to improve early detection and health equity. Through this training, CHWs gained critical cancer and genomics knowledge that was then applied to their primary roles.

Introduction: Although the prevalence of a pathogenic variant in the BRCA1 and BRCA2 genes is about 1:400 (0.25%) in the general population, the prevalence is as high as 1:40 (2.5%) among the Ashkenazi Jewish population. Despite cost-effective preventive measures for mutation carriers, Orthodox Jews constitute a cultural and religious group that requires different approaches to BRCA1 and BRCA2 genetic testing relative to other groups. This study analyzed a dialog of key stakeholders and community members to explore factors that influence decision-making about BRCA1 and BRCA2 genetic testing in the New York Orthodox Jewish community.

Methods: Qualitative research methods, based on Grounded Theory and Narrative Research, were utilized to analyze the narrative data collected from 49 key stakeholders and community members. A content analysis was conducted to identify themes; inter-rater reliability was 71%.

Results: Facilitators of genetic testing were a desire for preventive interventions and education, while barriers to genetic testing included negative emotions, feared impact on family/romantic relationships, cost, and stigma. Views differed on the role of religious leaders and healthcare professionals in medical decision-making. Education, health, and community were discussed as influential factors, and concerns were expressed about disclosure, implementation, and information needs.

Conclusion: This study elicited the opinions of Orthodox Jewish women (decision-makers) and key stakeholders (influencers) who play critical roles in the medical decision-making process. The findings have broad implications for engaging community stakeholders within faith-based or culturally distinct groups to ensure better utilization of healthcare services for cancer screening and prevention designed to improve population health.