RESUMO
Previous studies suggest compounds such as sulforaphane (SFN) derived from cruciferous vegetables may prevent prostate cancer development and progression. This study evaluated the effect of broccoli sprout extract (BSE) supplementation on blood histone deacetylase (HDAC) activity, prostate RNA gene expression, and tissue biomarkers (histone H3 lysine 18 acetylation (H3K18ac), HDAC3, HDAC6, Ki67, and p21). A total of 98 men scheduled for prostate biopsy were allocated into either BSE (200 µmol daily) or a placebo in our double-blind, randomized controlled trial. We used nonparametric tests to evaluate the differences of blood HDAC activity and prostate tissue immunohistochemistry biomarkers between treatment groups. Further, we performed RNA-Seq analysis on the prostate biopsies and identified 40 differentially expressed genes correlated with BSE treatment, including downregulation of two genes previously implicated in prostate cancer development, AMACR and ARLNC1. Although urine and plasma SFN isothiocyanates and individual SFN metabolites were statistically higher in the treatment group, our results did not show a significant difference in HDAC activity or prostate tissue biomarkers. This study indicates BSE supplementation correlates with changes in gene expression but not with several other prostate cancer biomarkers. More research is required to fully understand the chemopreventive effects of BSE supplementation on prostate cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Brassica , Quimioprevenção/métodos , Isotiocianatos/administração & dosagem , Próstata/efeitos dos fármacos , Neoplasias da Próstata/prevenção & controle , Idoso , Anticarcinógenos/administração & dosagem , Disponibilidade Biológica , Biópsia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Método Duplo-Cego , Histona Desacetilases/sangue , Humanos , Isotiocianatos/urina , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/dietoterapia , Neoplasias da Próstata/metabolismo , Racemases e Epimerases/metabolismo , Sulfóxidos , Produtos Vegetais/normasRESUMO
The potential for using widespread genetic testing to inform health care has become a viable option, particularly for heritable cancers. Yet, little is known about how to effectively communicate the benefits and risks of both personal genetic testing and participation in biorepositories that aid scientific advancements. Nationwide efforts are engaging communities in large genetic studies to better estimate the population-wide prevalence of heritable cancers but have been met with hesitance or declination to participate in some communities. To successfully engage an Oregon population in longitudinal research that includes predictive genetic testing for pathogenic or likely pathogenic variants associated with an increased risk for cancer, researchers conducted 35 focus groups (two of which were held in Spanish) in 24 of Oregon's 36 counties to better understand knowledge and attitudes related to genetic testing and willingness to participate in longitudinal genetic research. A total of 203 adults (mean = 45.6 years; range 18-88), representing a range of education levels and prior knowledge of genetic research, participated in the focus groups. The majority (85%) of participants reported personal or family diagnoses of cancer (e.g., self, family, friends). A majority (87%) also reported a strong interest in cancer genetic testing and receiving genetic information about themselves. Nearly all focus groups (94%, 33 of 35 sites) included participant discussion citing their families (e.g., children, close relatives, and extended family members) as key motivators for participation in genetic research. For example, participants reported interest in increasing personal knowledge about their own and their families' cancer risks in order to respond proactively, if a pathogenic variant was found. While most focus groups (94%, 33 of 35 sites) included participant discussion describing barriers to predictive genetic, testing such as concerns about outcomes, the desire to learn about health risks in oneself mitigated or outweighed those fears for many participants. Other commonly reported concerns were related to potential mistrust of insurance companies, researchers, or institutions, or lack of knowledge about genetics, genetic testing, or genetic research. Participants, particularly in rural areas, highlighted critical factors for research recruitment, such as trust, personal interaction, public education about genetic research, and clear communication about study goals and processes. Our statewide findings reflect that public interest in predictive cancer genetic testing and cancer genetic research can surpass lack of knowledge of the complex topics, particularly when benefits for self and family are emphasized and when study considerations are well articulated.
Assuntos
Testes Genéticos/métodos , Neoplasias/diagnóstico , Adulto , Criança , Família , Feminino , Grupos Focais , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Neoplasias/genética , OregonRESUMO
Animal and human studies suggest fish oil and green tea may have protective effect on prostate cancer. Fatty acid synthase (FAS) has been hypothesized to be linked to chemoprotective effects of both compounds. This study evaluated the independent and joint effects of fish oil (FO) and green tea supplement (epigallocatechin-3-gallate, EGCG) on FAS and Ki-67 levels in prostate tissue. Through a double-blinded, randomized controlled trial with 2 × 2 factorial design, 89 men scheduled for repeat prostate biopsy following an initial negative prostate biopsy were randomized into either FO alone (1.9 g DHA + EPA/day), EGCG alone (600 mg/day), a combination of FO and EGCG, or placebo. We used linear mixed-effects models to test the differences of prostate tissue FAS and Ki-67 by immunohistochemistry between pre- and post-intervention within each group, as well as between treatment groups. Results did not show significant difference among treatment groups in pre-to-post-intervention changes of FAS (P = 0.69) or Ki-67 (P = 0.26). Comparing placebo group with any of the treatment groups, we did not find significant difference in FAS or Ki-67 changes (all P > 0.05). Results indicate FO or EGCG supplementation for a short duration may not be sufficient to produce biologically meaningful changes in FAS or Ki-67 levels in prostate tissue.
Assuntos
Catequina/análogos & derivados , Ácido Graxo Sintase Tipo I/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Próstata/enzimologia , Idoso , Biópsia , Catequina/sangue , Catequina/farmacologia , Suplementos Nutricionais , Ácidos Graxos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/efeitos dos fármacosRESUMO
PURPOSE: The authors describe a rural community hospital's approach to lung cancer screening using low-dose CT (LDCT) to address the high incidence of lung cancer mortality. METHODS: An implementation project was conducted, documenting planning, education, and restructuring processes to implement a lung cancer screening program using LDCT in a rural community hospital (population 64,917, Rural-Urban Continuum Code 5) located in a region with the highest lung cancer mortality in Oregon. The hospital and community partners organized the implementation project around five recommendations for an efficient and effective lung cancer screening program that accurately identifies high-risk patients, facilitates timely access to screening, provides appropriate follow-up care, and offers smoking cessation support. RESULTS: Over a 3-year period (2018-2020), 567 LDCT scans were performed among a high-risk population. The result was a 4.8-fold increase in the number of LDCT scans from 2018 to 2019 and 54% growth from 2019 to 2020. The annual adherence rate increased from 51% in 2019 to 59.6% in 2020. Cancer was detected in 2.11% of persons scanned. Among the patients in whom lung cancer was detected, the majority of cancers (66.6%) were categorized as stage I or II. CONCLUSIONS: This rural community hospital's approach involved uniting primary care, specialty care, and community stakeholders around a single goal of improving lung cancer outcomes through early detection. The implementation strategy was intentionally organized around five recommendations for an effective and efficient lung cancer screening program and involved planning, education, and restructuring processes. Significant stakeholder involvement on three separate committees ensured that the program's design was relevant to local community contexts and patient centered. As a result, the screening program's reach and adherence increased each year of the 3-year pilot program.