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1.
Nat Genet ; 56(5): 809-818, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38671320

RESUMO

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals.


Assuntos
Carcinoma de Células Renais , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Renais , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Humanos , Neoplasias Renais/genética , Carcinoma de Células Renais/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Estudos de Casos e Controles , População Branca/genética
2.
Artigo em Inglês | MEDLINE | ID: mdl-38388859

RESUMO

PURPOSE: Metastatic breast cancer (MBC) patients often face substantial financial burden due to prolonged and expensive therapy. However, in-depth experiences of financial burden among MBC patients are not well understood. METHODS: Qualitative interviews were conducted to describe the experiences of financial burden for MBC patients, focusing on the drivers of financial burden, their experience using their health insurance, accessing financial assistance, and any resulting cost-coping behaviors. Interviews were transcribed and qualitatively analyzed using a descriptive phenomenological approach to thematic analysis. RESULTS: A total of n = 11 MBC patients or caregiver representatives participated in the study. MBC patients were on average 50.2 years of age (range: 28-65) and 72.7% non-Hispanic White. MBC patients were diagnosed as metastatic an average of 3.1 years (range: 1-9) before participating in the study. Qualitative analysis resulted in four themes including (1) causes of financial burden, (2) financial assistance mechanisms, (3) health insurance and financial burden, and (4) cost-coping behaviors. Both medical and non-medical costs drove financial burden among participants. All participants reported challenges navigating their health insurance and applying for financial assistance. Regardless of gaining access to assistance, financial burden persisted for nearly all patients and resulted in cost-coping behaviors. CONCLUSION: Our findings suggest that current systems for health insurance and financial assistance are complex and difficult to meet patient needs. Even when MBC patients accessed assistance, excess financial burden persisted necessitating use of financial coping-behaviors such as altering medication use, maintaining employment, and taking on debt.

3.
Commun Biol ; 7(1): 41, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182727

RESUMO

Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10-6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10-8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10-6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.


Assuntos
Linfoma de Burkitt , Infecções por Vírus Epstein-Barr , Criança , Humanos , Linfoma de Burkitt/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Cadeias alfa de HLA-DQ/genética
4.
Am J Hematol ; 99(1): 113-123, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38009642

RESUMO

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that significantly contributes to childhood cancer burden in sub-Saharan Africa. Plasmodium falciparum, which causes malaria, is geographically associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria-such as the sickle cell trait variant, HBB-rs334(T)-also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome-scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB-rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628-0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533-0.885; p = .0037). ABO-rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379-0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk.


Assuntos
Linfoma de Burkitt , Malária Falciparum , Malária , Traço Falciforme , Humanos , África Oriental , Alelos , Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/genética , Malária Falciparum/epidemiologia , Malária Falciparum/genética , Malária Falciparum/complicações , Traço Falciforme/epidemiologia , Traço Falciforme/genética , Traço Falciforme/complicações , Nectinas/metabolismo
5.
Nat Commun ; 14(1): 8081, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057307

RESUMO

In high-income countries, mosaic chromosomal alterations in peripheral blood leukocytes are associated with an elevated risk of adverse health outcomes, including hematologic malignancies. We investigate mosaic chromosomal alterations in sub-Saharan Africa among 931 children with Burkitt lymphoma, an aggressive lymphoma commonly characterized by immunoglobulin-MYC chromosomal rearrangements, 3822 Burkitt lymphoma-free children, and 674 cancer-free men from Ghana. We find autosomal and X chromosome mosaic chromosomal alterations in 3.4% and 1.7% of Burkitt lymphoma-free children, and 8.4% and 3.7% of children with Burkitt lymphoma (P-values = 5.7×10-11 and 3.74×10-2, respectively). Autosomal mosaic chromosomal alterations are detected in 14.0% of Ghanaian men and increase with age. Mosaic chromosomal alterations in Burkitt lymphoma cases include gains on chromosomes 1q and 8, the latter spanning MYC, while mosaic chromosomal alterations in Burkitt lymphoma-free children include copy-neutral loss of heterozygosity on chromosomes 10, 14, and 16. Our results highlight mosaic chromosomal alterations in sub-Saharan African populations as a promising area of research.


Assuntos
Linfoma de Burkitt , Masculino , Criança , Humanos , Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Gana , Aberrações Cromossômicas , Leucócitos/patologia , Imunoglobulinas/genética , Translocação Genética
6.
Front Health Serv ; 3: 1148887, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37941608

RESUMO

Background: Financial navigation (FN) is an evidence-based intervention designed to address financial toxicity for cancer patients. FN's success depends on organizations' readiness to implement and other factors that may hinder or support implementation. Tailored implementation strategies can support practice change but must be matched to the implementation context. We assessed perceptions of readiness and perceived barriers and facilitators to successful implementation among staff at nine cancer care organizations (5 rural, 4 non-rural) recruited to participate in the scale-up of a FN intervention. To understand differences in the pre-implementation context and inform modifications to implementation strategies, we compared findings between rural and non-rural organizations. Methods: We conducted surveys (n = 78) and in-depth interviews (n = 73) with staff at each organization. We assessed perceptions of readiness using the Organizational Readiness for Implementing Change (ORIC) scale. In-depth interviews elicited perceived barriers and facilitators to implementing FN in each context. We used descriptive statistics to analyze ORIC results and deductive thematic analysis, employing a codebook guided by the Consolidated Framework for Implementation Research (CFIR), to synthesize themes in barriers and facilitators across sites, and by rurality. Results: Results from the ORIC scale indicated strong perceptions of organizational readiness across all sites. Staff from rural areas reported greater confidence in their ability to manage the politics of change (87% rural, 76% non-rural) and in their organization's ability to support staff adjusting to the change (96% rural, 75% non-rural). Staff at both rural and non-rural sites highlighted factors reflective of the Intervention Characteristics (relative advantage) and Implementation Climate (compatibility and tension for change) domains as facilitators. Although few barriers to implementation were reported, differences arose between rural and non-rural sites in these perceived barriers, with non-rural staff more often raising concerns about resistance to change and compatibility with existing work processes and rural staff more often raising concerns about competing time demands and limited resources. Conclusions: Staff across both rural and non-rural settings identified few, but different, barriers to implementing a novel FN intervention that they perceived as important and responsive to patients' needs. These findings can inform how strategies are tailored to support FN in diverse oncology practices.

7.
JCO Oncol Pract ; 19(8): 654-661, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37294912

RESUMO

PURPOSE: Financial navigation services support patients with cancer and address the direct and indirect financial burden of cancer diagnosis and treatment. These services are commonly delivered through a variety of frontline oncology support personnel (FOSP) including navigators, social workers, supportive care providers, and other clinic staff, but the perspective of FOSPs is largely absent from current literature on financial burden in oncology. We surveyed a national sample of FOSPs to understand their perspectives on patient financial burden, resource availability, and barriers and facilitators to assisting patients with cancer-related financial burden. METHODS: We used Qualtrics online survey software and recruited participants using multiple professional society and interest group mailing lists. Categorical responses were described using frequencies, distributions of numeric survey responses were described using the median and IQR, and two open-ended survey questions were categorized thematically using a priori themes, allowing additional emergent themes. RESULTS: Two hundred fourteen FOSPs completed this national survey. Respondents reported a high awareness of patient financial burden and felt comfortable speaking to patients about financial concerns. Patient assistance resources were commonly available, but only 15% described resources as sufficient for the observed needs. A substantial portion of respondents reported moral distress related to this lack of resources. CONCLUSION: FOSPs, who already have requisite knowledge and comfort in discussing patient financial needs, are a critical resource for mitigating cancer-related financial burden. Interventions should leverage this resource but prioritize transparency and efficiency to reduce the administrative and emotional toll on the FOSP workforce and reduce the risk of burnout.


Assuntos
Estresse Financeiro , Neoplasias , Humanos , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias/epidemiologia , Neoplasias/terapia , Oncologia , Emoções
8.
Cancer Med ; 12(10): 11930-11940, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37148550

RESUMO

BACKGROUND: Little is known about the heterogeneous nature of financial hardship in younger patients with metastatic disease and the extent to which insurance protects against it. We examine the association between insurance status and multidimensional indicators of financial hardship in a national sample of women with metastatic breast cancer. METHODS: We conducted a national, retrospective online survey in partnership with the Metastatic Breast Cancer Network. Eligible participants were ≥18 years, diagnosed with metastatic breast cancer, and able to respond in English. We estimated multivariate generalized linear models predicting two distinct dimensions of financial hardship-financial insecurity (the ability to afford care and living costs) and financial distress (the extent of emotional/psychological distress experienced due to costs)-as a function of insurance status. RESULTS: Participants responded from 41 states (N = 1054; median age: 44 years). Overall, 30% were uninsured. Financial insecurity was more frequently reported by uninsured respondents. In adjusted analyses, uninsured participants were more likely than insured participants to report contact by debt collectors (adjusted risk ratio [aRR]: 2.38 [2.06, 2.76]) and being unable to meet monthly expenses (aRR: 2.11 [1.68, 2.66]). Financial distress was reported more frequently by insured participants. For example, insured participants were more likely to worry about future financial problems due to cancer and distress about lack of cost transparency. After adjustment, uninsured participants remained about half as likely as insured participants to report financial distress. CONCLUSIONS: Young adult women with metastatic cancer reported a high burden of financial toxicity. Importantly, insurance does not protect against financial distress; however, the uninsured are the most materially vulnerable.


Assuntos
Neoplasias da Mama , Pessoas sem Cobertura de Seguro de Saúde , Humanos , Feminino , Adulto Jovem , Estados Unidos/epidemiologia , Adulto , Seguro Saúde , Estresse Financeiro , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Estudos Retrospectivos , Gastos em Saúde
9.
Am J Hum Genet ; 110(3): 427-441, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36787739

RESUMO

Ewing sarcoma (EwS) is a rare bone and soft tissue malignancy driven by chromosomal translocations encoding chimeric transcription factors, such as EWSR1-FLI1, that bind GGAA motifs forming novel enhancers that alter nearby expression. We propose that germline microsatellite variation at the 6p25.1 EwS susceptibility locus could impact downstream gene expression and EwS biology. We performed targeted long-read sequencing of EwS blood DNA to characterize variation and genomic features important for EWSR1-FLI1 binding. We identified 50 microsatellite alleles at 6p25.1 and observed that EwS-affected individuals had longer alleles (>135 bp) with more GGAA repeats. The 6p25.1 GGAA microsatellite showed chromatin features of an EWSR1-FLI1 enhancer and regulated expression of RREB1, a transcription factor associated with RAS/MAPK signaling. RREB1 knockdown reduced proliferation and clonogenic potential and reduced expression of cell cycle and DNA replication genes. Our integrative analysis at 6p25.1 details increased binding of longer GGAA microsatellite alleles with acquired EWSR-FLI1 to promote Ewing sarcomagenesis by RREB1-mediated proliferation.


Assuntos
Neoplasias Ósseas , Sarcoma de Ewing , Humanos , Alelos , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteína Proto-Oncogênica c-fli-1/genética , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteína EWS de Ligação a RNA/genética , Proteína EWS de Ligação a RNA/metabolismo , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patologia
10.
J Adolesc Young Adult Oncol ; 12(5): 735-743, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36706031

RESUMO

Purpose: The purpose of this study was to identify resource needs and preferences of young adult cancer survivors (YAs) during the transition from active treatment to survivorship care to inform tailored care tools to support YAs during this period. Methods: A mixed methods study following a sequential explanatory approach was conducted among YAs between the ages of 15 and 39. Online surveys were distributed to assess participant information and resource needs, and responses were further explored during virtual focus group and interview discussions. Frequencies and proportions were calculated to identify quantitative resource needs, and a descriptive qualitative approach was used to gather and analyze qualitative data. Results: Thirty-one participants completed the online surveys, and 27 participated in qualitative data collection. The top resource needs identified in the surveys and discussed in focus groups and interviews were (1) fear of recurrence, (2) sleep and fatigue, (3) anxiety, (4) nutrition, (5) physical activity, and (6) finances. Emergent themes identified during transcript analyses included the need for (1) tailored, customizable resources, (2) connection with other survivors, (3) tools to guide conversations about cancer, (4) clarity in what to expect during treatment and survivorship, and (5) consistent and equitable care in YA oncology. Conclusions: Participants identified six important information needs in addition to an overarching need for tailored support and equitable distribution of resources while transitioning into early survivorship. Thus, tailored interventions are needed to enhance the distribution of YA-centered resources, improve equity in YA cancer care, and connect YAs with peer survivors.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Adulto Jovem , Adolescente , Adulto , Sobrevivência , Sobreviventes , Neoplasias/terapia , Grupos Focais
11.
Trials ; 23(1): 839, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192802

RESUMO

BACKGROUND: Almost half of the patients with cancer report cancer-related financial hardship, termed "financial toxicity" (FT), which affects health-related quality of life, care retention, and, in extreme cases, mortality. This increasingly prevalent hardship warrants urgent intervention. Financial navigation (FN) targets FT by systematically identifying patients at high risk, assessing eligibility for existing resources, clarifying treatment cost expectations, and working with patients and caregivers to develop a plan to cope with cancer costs. This trial seeks to (1) identify FN implementation determinants and implementation outcomes, and (2) evaluate the effectiveness of FN in improving patient outcomes. METHODS: The Lessening the Impact of Financial Toxicity (LIFT) study is a multi-site Phase 2 clinical trial. We use a pre-/post- single-arm intervention to examine the effect of FN on FT in adults with cancer. The LIFT trial is being conducted at nine oncology care settings across North Carolina in the United States. Sites vary in geography (five rural, four non-rural), size (21-974 inpatient beds), and ownership structure (governmental, non-profit). The study will enroll 780 patients total over approximately 2 years. Eligible patients must be 18 years or older, have a confirmed cancer diagnosis (any type) within the past 5 years or be living with advanced disease, and screen positive for cancer-related financial distress. LIFT will be delivered by full- or part-time financial navigators and consists of 3 components: (1) systematic FT screening identification and comprehensive intake assessment; (2) connecting patients experiencing FT to financial support resources via trained oncology financial navigators; and (3) ongoing check-ins and electronic tracking of patients' progress and outcomes by financial navigators. We will measure intervention effectiveness by evaluating change in FT (via the validated Comprehensive Score of Financial Toxicity, or COST instrument) (primary outcome), as well as health-related quality of life (PROMIS Global Health Questionnaire), and patient-reported delayed or forgone care due to cost. We also assess patient- and stakeholder-reported implementation and service outcomes post-intervention, including uptake, fidelity, acceptability, cost, patient-centeredness, and timeliness. DISCUSSION: This study adds to the growing evidence on FN by evaluating its implementation and effectiveness across diverse oncology care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04931251. Registered on June 18, 2021.


Assuntos
Neoplasias , Qualidade de Vida , Adulto , Estresse Financeiro , Custos de Cuidados de Saúde , Humanos , Oncologia , Estudos Multicêntricos como Assunto , Neoplasias/terapia
12.
JCO Oncol Pract ; 18(9): e1392-e1406, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35549521

RESUMO

PURPOSE: Patients with cancer are at heightened risk of experiencing financial hardship. Financial navigation (FN) is an evidence-based approach for identifying and addressing patient and caregiver financial needs. In preparation for the implementation of a multisite FN intervention, we describe existing processes (ie, events and actions) and mechanisms (ie, how events work together) connecting patients to financial assistance, comparing rural and nonrural practices. METHODS: We conducted in-depth, semistructured interviews with stakeholders (ie, administrators, providers, and staff) at each of the 10 oncology care sites across a single state (five rural and five nonrural practices). We developed process maps for each site and analyzed stakeholder perspectives using thematic analysis. After reporting findings back to stakeholders, we synthesized themes and process maps across rural and nonrural sites separately. RESULTS: Eighty-three stakeholders were interviewed. We identified six core elements of existing financial assistance processes across all sites: distress screening (including financial concerns), referrals, resource connection points, and pharmaceutical, insurance, and community/foundation resources. Processes differed by rurality; however, facilitators and barriers to identifying and addressing patient financial needs were consistent. Open communication between staff, providers, patients, and caregivers was a primary facilitator. Barriers included insufficient staff resources, challenges in routinely identifying needs, inadequate preparation of patients for anticipated medical costs, and limited tracking of resource availability and eligibility. CONCLUSION: This study identified a clear need for systematic implementation of oncology FN to equitably address patient and caregiver financial hardship. Results have informed our current efforts to implement a multisite FN intervention, which involves comprehensive financial toxicity screening and systematization of intake and referrals.


Assuntos
Oncologia , Neoplasias , Definição da Elegibilidade , Humanos , Encaminhamento e Consulta , População Rural
13.
Front Health Serv ; 2: 958831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36925862

RESUMO

Background: Lessening the Impact of Financial Toxicity (LIFT) is an intervention designed to address financial toxicity (FT) and improve cancer care access and outcomes through financial navigation (FN). FN identifies patients at risk for FT, assesses eligibility for financial support, and develops strategies to cope with those costs. LIFT successfully reduced FT and improved care access in a preliminary study among patients with high levels of FT in a single large academic cancer center. Adapting LIFT requires distinguishing between core functions (components that are key to its implementation and effectiveness) and forms (specific activities that carry out core functions). Our objective was to complete the first stage of adaptation, identifying LIFT core functions. Methods: We reviewed LIFT's protocol and internal standard-operating procedures. We then conducted 45-90 min in-depth interviews, using Kirk's method of identifying core functions, with key LIFT staff (N = 8), including the principal investigators. Interviews focused on participant roles and intervention implementation. Recorded interviews were transcribed verbatim. Using ATLAS.ti and a codebook based on the Model for Adaptation Design and Impact, we coded interview transcripts. Through thematic analysis, we then identified themes related to LIFT's intervention and implementation core functions. Two report back sessions with interview participants were incorporated to further refine themes. Results: Six intervention core functions (i.e., what makes LIFT effective) and five implementation core functions (i.e., what facilitated LIFT's implementation) were identified to be sufficient to reduce FT. Intervention core functions included systematically cataloging knowledge and tracking patient-specific information related to eligibility criteria for FT relief. Repeat contacts between the financial navigator and participant created an ongoing relationship, removing common barriers to accessing resources. Implementation core functions included having engaged sites with the resources and willingness necessary to implement FN. Developing navigators' capabilities to implement LIFT-through training, an established case management system, and connections to peer navigators-were also identified as implementation core functions. Conclusion: This study adds to the growing evidence on FN by characterizing intervention and implementation core functions, a critical step toward promoting LIFT's implementation and effectiveness.

14.
PLoS One ; 15(9): e0237792, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881892

RESUMO

BACKGROUND: Ewing sarcoma (EwS) is a rare, aggressive solid tumor of childhood, adolescence and young adulthood associated with pathognomonic EWSR1-ETS fusion oncoproteins altering transcriptional regulation. Genome-wide association studies (GWAS) have identified 6 common germline susceptibility loci but have not investigated low-frequency inherited variants with minor allele frequencies below 5% due to limited genotyped cases of this rare tumor. METHODS: We investigated the contribution of rare and low-frequency variation to EwS susceptibility in the largest EwS genome-wide association study to date (733 EwS cases and 1,346 unaffected controls of European ancestry). RESULTS: We identified two low-frequency variants, rs112837127 and rs2296730, on chromosome 20 that were associated with EwS risk (OR = 0.186 and 2.038, respectively; P-value < 5×10-8) and located near previously reported common susceptibility loci. After adjusting for the most associated common variant at the locus, only rs112837127 remained a statistically significant independent signal (OR = 0.200, P-value = 5.84×10-8). CONCLUSIONS: These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk. IMPACT: Motivate future targeted sequencing studies for a comprehensive evaluation of low-frequency and rare variation around common EwS susceptibility loci.


Assuntos
Loci Gênicos , Predisposição Genética para Doença , Variação Genética , Células Germinativas/metabolismo , Sarcoma de Ewing/genética , Estudo de Associação Genômica Ampla , Humanos , Desequilíbrio de Ligação/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética
15.
Breast Cancer Res Treat ; 179(1): 207-215, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31555940

RESUMO

PURPOSE: Little is known about racial variations in the financial impact of cancer care. Using data from a national survey of racially diverse patients with metastatic breast cancer, we examined racial/ethnic patterns in employment and cost-management (i.e., financial coping) behaviors. METHODS: We conducted an online survey of patients with metastatic breast cancer. Participants reported on socio-demographic characteristics, employment, and financial coping behaviors. We employed adjusted modified Poisson regressions to evaluate racial/ethnic differences in changes in work for pay and financial coping. RESULTS: Our analysis included 1052 respondents from 41 states, including Non-Hispanic Blacks (NHB, 9%), Hispanics (7%), Asians/Pacific Islanders/Native Hawaiians (API/NH, 10%), American Indians/Alaskan Natives (AI/AN, 8%), and Non-Hispanic Whites (NHW, 66%). In adjusted analyses comparing NHWs with patients of color, patients of color were more likely to take unpaid leave (NHB Adjusted Risk Ratio [ARR] = 2.27; 95% CI 1.54, 3.34), take paid leave (Hispanic ARR = 2.27; 95% CI 1.54, 1.29), stop work (AI/AN ARR = 1.22; 95% CI 1.05, 1.41), and reduce work hours (AI/AN ARR = 1.33; 95% CI 1.14, 1.57). Patients of color were more likely than NHWs to stop treatment (NHB ARR = 1.22; 95% CI 1.08, 1.39), borrow money from friends/family (Hispanic ARR = 1.75; 95% CI 1.25, 2.44), skip other medical bills (API/NH ARR = 2.02; 95% CI 1.54, 2.63), and skip non-medical bills (AI/AN ARR = 1.67 95% CI 1.06, 2.63). Non-Hispanic Whites more commonly reported using savings or skipping a vacation to help manage costs. CONCLUSIONS: Racial/ethnic differences exist in employment changes and financial coping among metastatic breast cancer patients, with patients of color experiencing worse consequences. Equity must be a guiding principle in strategies addressing financial burden during cancer care.


Assuntos
Neoplasias da Mama/economia , Neoplasias da Mama/etnologia , Emprego/estatística & dados numéricos , Adulto , Neoplasias da Mama/epidemiologia , Emprego/economia , Feminino , Gastos em Saúde , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Licença Médica/economia , Licença Médica/estatística & dados numéricos , Estados Unidos/etnologia
16.
Psychooncology ; 28(9): 1854-1861, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31260139

RESUMO

OBJECTIVE: With a steadily increasing number of Latino/a cancer survivors, there is a need for supportive care programs for this underserved survivor subgroup. METHODS: In this study, the authors culturally adapted an evidence-based survivorship program, Cancer Transitions: Moving Beyond Treatment (CT) for this population. Guided by Barrera and Castro's heuristic model for cultural adaptation of interventions, we conducted five focus groups (FG) among Latino/a cancer survivors (n = 54) in several US sites to inform the preliminary adaptation of program materials. We conducted four additional FGs (n = 38) to obtain feedback on adapted materials. RESULTS: Common themes from initial FGs were related to program delivery and logistics, and general recommendations for CT modification. Program adaptations addressed information needs, including health care system navigation, employment concerns, and sexuality. Other adaptations included an emphasis on family, spirituality, culturally appropriate translation and features, and role plays. Participants in the second round of FGs confirmed adaptations incorporated earlier findings and suggested additional refinements. CONCLUSION: This project helps guide the cultural adaptation of survivorship programs for Latino/a cancer survivors.


Assuntos
Sobreviventes de Câncer/psicologia , Assistência à Saúde Culturalmente Competente/organização & administração , Hispânico ou Latino/psicologia , Desenvolvimento de Programas , Sobreviventes de Câncer/estatística & dados numéricos , Feminino , Grupos Focais , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino
17.
Nephrology (Carlton) ; 24(5): 550-556, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29781238

RESUMO

AIM: Formation of autogenous arteriovenous fistula (AVF) in patients with chronic kidney disease (CKD) is complicated by a high primary failure rate. We hypothesized that early (months to years before AVF creation) Venous Preservation Scan (VPS) followed by vasculature preservation is effective in protecting the patient's best 'for fistula' vasculature. This study was performed to evaluate the impact of VPS on AVF outcomes. METHODS: The case records of 123 patients who underwent ultrasound mapping for AVF creation in a district hospital were reviewed. Ninety-seven were VPS and 26 were Routine Pre-Operative Planning Scan (RPOPS) performed immediately prior to surgery. Outcomes of 21 patients who went onto AVF creation in the VPS group were compared to 23 patients in the RPOPS group. RESULTS: Success and complication rates for AVF placement in patients who underwent VPS versus RPOPS were 100% versus 91.3% (P = 0.27) and 0 versus 8.7% (P = 0.23). A greater proportion of AVF created following RPOPS required intervention before maturation (47.6% vs 19%, P = 0.05). The median primary patency of AVF created following VPS versus RPOPS was 492 (IQR 222, 1219) versus 169 (IQR 116, 414) days (P = 0.02). The cumulative patency did not differ between the two groups (median = 807 (IQR 499, 1308) versus 1059 (IQR 331, 1263) days, P = 0.26). CONCLUSIONS: This small study suggests that VPS may favourably influence the survival of primary AVF and reduce the need for assisted interventions. However, confirmation with larger randomized controlled trial is warranted.


Assuntos
Derivação Arteriovenosa Cirúrgica/métodos , Educação de Pacientes como Assunto/métodos , Diálise Renal , Insuficiência Renal Crônica/terapia , Ultrassonografia Doppler Dupla , Extremidade Superior/irrigação sanguínea , Veias/diagnóstico por imagem , Idoso , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Progressão da Doença , Feminino , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
18.
Nat Commun ; 9(1): 3184, 2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-30093639

RESUMO

Ewing sarcoma (EWS) is a pediatric cancer characterized by the EWSR1-FLI1 fusion. We performed a genome-wide association study of 733 EWS cases and 1346 unaffected individuals of European ancestry. Our study replicates previously reported susceptibility loci at 1p36.22, 10q21.3 and 15q15.1, and identifies new loci at 6p25.1, 20p11.22 and 20p11.23. Effect estimates exhibit odds ratios in excess of 1.7, which is high for cancer GWAS, and striking in light of the rarity of EWS cases in familial cancer syndromes. Expression quantitative trait locus (eQTL) analyses identify candidate genes at 6p25.1 (RREB1) and 20p11.23 (KIZ). The 20p11.22 locus is near NKX2-2, a highly overexpressed gene in EWS. Interestingly, most loci reside near GGAA repeat sequences and may disrupt binding of the EWSR1-FLI1 fusion protein. The high locus to case discovery ratio from 733 EWS cases suggests a genetic architecture in which moderate risk SNPs constitute a significant fraction of risk.


Assuntos
Perfilação da Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Sarcoma de Ewing/genética , Alelos , Proteínas de Ciclo Celular/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Genótipo , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio/genética , Humanos , Proteínas Nucleares , Proteínas de Fusão Oncogênica/genética , Polimorfismo de Nucleotídeo Único , Proteína Proto-Oncogênica c-fli-1/genética , Controle de Qualidade , Locos de Características Quantitativas , Proteína EWS de Ligação a RNA/genética , Risco , Sarcoma de Ewing/etnologia , Fatores de Transcrição/genética , População Branca , Proteínas de Peixe-Zebra
19.
Support Care Cancer ; 26(4): 1315-1321, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29124417

RESUMO

INTRODUCTION: As the cost of cancer treatment continues to rise, many patients are faced with significant emotional and financial burden. Oncology navigators guide patients through many aspects of care and therefore may be especially aware of patients' financial distress. Our objective was to explore navigators' perception of their patients' financial burden and their role in addressing financial needs. MATERIALS AND METHODS: We conducted a real-time online survey of attendees at an oncology navigators' association conference. Participants included lay navigators, oncology nurse navigators, community health workers, and social workers. Questions assessed perceived burden in their patient population and their role in helping navigate patients through financial resources. Answers to open-ended questions are reported using identified themes. RESULTS: Seventy-eight respondents participated in the survey, reporting that on average 75% of their patients experienced some degree of financial toxicity related to their cancer. Only 45% of navigators felt the majority of these patients were able to get some financial assistance, most often through assistance with medical costs (73%), subsidized insurance (36%), or non-medical expenses (31%). Commonly identified barriers for patients obtaining assistance included lack of resources (50%), lack of knowledge about resources (46%), and complex/duplicative paperwork (20%). CONCLUSION: Oncology navigators reported a high burden of financial toxicity among their patients but insufficient knowledge or resources to address this need. This study underscores the importance of improved training and coordination for addressing financial burden, and the need to address community and system-level barriers.


Assuntos
Custos de Cuidados de Saúde , Neoplasias/economia , Navegação de Pacientes , Humanos , Seguro Saúde , Medicaid , Oncologia , Neoplasias/psicologia , Inquéritos e Questionários , Estados Unidos
20.
Telemed J E Health ; 21(10): 793-800, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26431258

RESUMO

BACKGROUND: Group interventions are effective for addressing the transition from cancer treatment to survivorship but are not widely available outside of urban areas. In addition, minimal training is available for group facilitators outside of the mental healthcare discipline. Telehealth as a medium can facilitate conversation and interactive learning and make learning accessible to individuals in areas that lack resources for traditional classroom teaching. Little is known, however, regarding the feasibility and acceptability of a telehealth training program for group leaders. This project aimed to investigate the utility of a telehealth training program for the delivery of a copyrighted, manualized psychosocial group intervention, Cancer Transitions: Moving Beyond Treatment. MATERIALS AND METHODS: Nine group leaders attended one in-person orientation, four telehealth training classes, and four telehealth supervision sessions, completing self-report measures of content knowledge, quality satisfaction, and self-confidence. Following the completion of their last Cancer Transitions facilitation, group leaders participated in a focus group to provide qualitative feedback regarding their experiences in training for and leading the respective groups in eight urban and rural North Carolina communities. RESULTS: Group leaders rated the training program highly across the domains of content knowledge, quality satisfaction, and self-confidence. Satisfaction with the technology itself was equivocal. CONCLUSIONS: Telehealth represents a feasible avenue for training and supporting leaders of psychosocial interventions. In addition, telehealth is particularly well suited to the need for training group leaders in areas outside urban centers or academic communities.


Assuntos
Educação Médica Continuada/métodos , Pessoal de Saúde , Neoplasias/terapia , Telemedicina/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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