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1.
Cancer Epidemiol Biomarkers Prev ; 31(5): 982-990, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35247879

RESUMO

BACKGROUND: Racial disparities in prostate cancer incidence and mortality rates are considerable. We previously found in the Health Professionals Follow-up Study (HPFS) that African-American men had an 80% higher prostate cancer risk than White men. With 21 additional years of follow-up and four-fold increase in cases, we undertook a contemporary analysis of racial differences in prostate cancer incidence and mortality in HPFS. METHODS: For 47,679 men, we estimated HRs and 95% confidence intervals (CI) for the association between race and risk of prostate cancer through 2016 using Cox proportional hazards regression. Multivariable models (mHR) were adjusted for lifestyle, diet, family history, and PSA screening collected on biennial questionnaires. RESULTS: 6,909 prostate cancer cases were diagnosed in White, 89 in African-American, and 90 in Asian-American men. African-Americans had higher prostate cancer incidence (mHR = 1.31; 95% CI, 1.06-1.62) and mortality (mHR = 1.67; 95% CI, 1.00-2.78), and lower PSA screening prevalence than White men. The excess risk was greater in the pre-PSA screening era (HR = 1.68; 95% CI, 1.14-2.48) than the PSA screening era (HR = 1.20; 95% CI, 0.93-1.56). Asian-Americans had lower prostate cancer risk (mHR = 0.74; 95% CI, 0.60-0.92), but similar risk of fatal disease compared with white men. CONCLUSIONS: Racial differences in prostate cancer incidence and mortality in HPFS are not fully explained by differences in lifestyle, diet, family history, or PSA screening. IMPACT: Additional research is necessary to address the disproportionately higher rates of prostate cancer in African-American men.


Assuntos
Detecção Precoce de Câncer , Neoplasias da Próstata , Dieta , Seguimentos , Humanos , Estilo de Vida , Masculino , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia
3.
Mol Cancer Res ; 19(3): 475-484, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33168599

RESUMO

Gleason score, a measure of prostate tumor differentiation, is the strongest predictor of lethal prostate cancer at the time of diagnosis. Metabolomic profiling of tumor and of patient serum could identify biomarkers of aggressive disease and lead to the development of a less-invasive assay to perform active surveillance monitoring. Metabolomic profiling of prostate tissue and serum samples was performed. Metabolite levels and metabolite sets were compared across Gleason scores. Machine learning algorithms were trained and tuned to predict transformation or differentiation status from metabolite data. A total of 135 metabolites were significantly different (P adjusted < 0.05) in tumor versus normal tissue, and pathway analysis identified one sugar metabolism pathway (P adjusted = 0.03). Machine learning identified profiles that predicted tumor versus normal tissue (AUC of 0.82 ± 0.08). In tumor tissue, 25 metabolites were associated with Gleason score (unadjusted P < 0.05), 4 increased in high grade while the remainder were enriched in low grade. While pyroglutamine and 1,5-anhydroglucitol were correlated (0.73 and 0.72, respectively) between tissue and serum from the same patient, no metabolites were consistently associated with Gleason score in serum. Previously reported as well as novel metabolites with differing abundance were identified across tumor tissue. However, a "metabolite signature" for Gleason score was not obtained. This may be due to study design and analytic challenges that future studies should consider. IMPLICATIONS: Metabolic profiling can distinguish benign and neoplastic tissues. A novel unsupervised machine learning method can be utilized to achieve this distinction.


Assuntos
Aprendizado de Máquina/normas , Metabolômica/métodos , Neoplasias da Próstata/genética , Feminino , Humanos , Masculino , Gradação de Tumores
4.
Cancer Epidemiol Biomarkers Prev ; 29(7): 1374-1380, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32503813

RESUMO

BACKGROUND: Although there are considerable racial and ethnic disparities in prostate cancer incidence and mortality in the United States and globally, clinical trials often do not reflect disease incidence across racial and ethnic subgroups. This study aims to comprehensively review the reporting of race and ethnicity data and the representation of race and ethnicity across prostate cancer treatment-, prevention-, and screening-based clinical trials. METHODS: Seventy-two global phase III and IV prevention, screening, and treatment prostate cancer clinical trials with enrollment start dates between 1987 and 2016 were analyzed in this study, representing a total of 893,378 individual trial participants. Availability and representation of race and ethnicity data by trial funding type, temporal changes in the racial/ethnic diversity of participants, and geographic representation of countries were assessed. RESULTS: Of the 72 trials analyzed, 59 (81.9%) had available race data, and 11 (15.3%) of these trials additionally reported ethnicity. Of the trials reporting data, participants were overwhelmingly white men (with the highest proportion in U.S. nonpublicly funded trials), comprising over 96% of the study population. The proportion of white participants in prostate cancer clinical trials has remained at over 80% since 1990. Geographically, Africa and the Caribbean were particularly underrepresented with only 3% of countries included. CONCLUSIONS: Trial participants continue to be majority white despite the known racial disparities in prostate cancer clinical outcomes. IMPACT: Current and future trials must use novel recruitment strategies to ensure enrollment of underrepresented men. Targeting the inclusion of African and Caribbean medical centers is crucial to achieve equity in representation.


Assuntos
Neoplasias da Próstata/epidemiologia , Ensaios Clínicos como Assunto , Humanos , Masculino
5.
Cancer Epidemiol Biomarkers Prev ; 29(6): 1229-1236, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32277004

RESUMO

BACKGROUND: The association between male pattern baldness and prostate cancer has been inconsistent. We prospectively investigated the association between baldness at age 45 and prostate cancer risk in the Health Professionals Follow-up Study (HPFS), focusing on clinical and molecular markers. METHODS: Baldness was self-reported on the 1992 questionnaire using the modified Norwood-Hamilton scale prior to diagnosis. We estimated HRs between baldness and prostate cancer risk among 36,760 men, with follow-up through 2014. We also investigated whether baldness was associated with prostate cancer defined by tumor protein expression of androgen receptor and the presence of the TMPRSS2:ERG fusion. RESULTS: During 22 years, 5,157 prostate cancer cases were identified. Fifty-six percent of the men had either frontal or vertex baldness. No significant associations were found between baldness and prostate cancer risk. Among men younger than 60 years, there was a statistically significant association between frontal and severe vertex baldness and overall prostate cancer (HR: 1.74; 95% confidence interval: 1.23-2.48). Baldness was not significantly associated with expression of molecular subtypes defined by AR and TMPRSS2:ERG IHC of prostate tumors. CONCLUSIONS: This study showed no association between baldness at age 45 and prostate cancer risk, overall or for clinical or molecular markers. The association between baldness and overall prostate cancer among younger men is intriguing, but caution is warranted when interpreting this finding. IMPACT: The null findings from this large cohort study, together with previous literature's inconclusive findings across baldness patterns, suggest that baldness is not a consistent biomarker for prostate cancer risk or progression.


Assuntos
Alopecia/complicações , Neoplasias da Próstata/fisiopatologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Int J Cancer ; 144(10): 2377-2380, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30242839

RESUMO

We previously observed a positive association between seropositivity for the parasite Trichomonas vaginalis and risk of clinically significant prostate cancer at diagnosis. Here, we examined whether T. vaginalis seropositivity was associated with increased prostate cancer-specific or all-cause mortality among prostate cancer patients. We studied 736 men with prostate cancer from the Physicians' Health Study (PHS) and 749 men with prostate cancer from the Health Professionals Follow-Up Study (HPFS). We used Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between T. vaginalis serostatus and progression to death from prostate cancer and from all causes. In PHS, 423 men died of any cause during a median follow-up of 13.8 years from the date of cancer diagnosis, among whom 131 died of prostate cancer. In HPFS, there were 287 deaths, including 77 deaths from prostate cancer, during a median follow-up of 12.8 years. We found no association between T. vaginalis serostatus and either prostate cancer mortality or all-cause mortality in either the PHS or HPFS. While previous studies suggest a possible role for T. vaginalis in the development of clinically significant prostate cancer, our findings do not support the hypothesis that T. vaginalis serostatus is associated with mortality among prostate cancer patients.


Assuntos
Neoplasias da Próstata/etiologia , Neoplasias da Próstata/mortalidade , Vaginite por Trichomonas/complicações , Trichomonas vaginalis/patogenicidade , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/parasitologia , Próstata/patologia , Neoplasias da Próstata/parasitologia , Neoplasias da Próstata/patologia , Fatores de Risco , Vaginite por Trichomonas/patologia
7.
Cancer Epidemiol Biomarkers Prev ; 27(10): 1231-1233, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30108097

RESUMO

Background: In a case-control study, aspirin use was associated with a lower risk of a common prostate cancer molecular subtype, the TMPRSS2:ERG gene fusion. We sought to validate this finding in a prospective cohort.Methods: In the Health Professionals Follow-up Study, 49,395 men reported on aspirin use on biennial questionnaires and were followed for prostate cancer incidence over 23 years. TMPRSS2:ERG status was assessed by IHC for presence of ERG on archival tumor specimens for 912 patients with prostate cancer, of whom 48% were ERG-positive.Results: In multivariable models, we found no association between regular use of aspirin and risk of ERG-positive prostate cancer (HR, 1.02; 95% confidence interval, 0.85-1.23), nor any association with duration or frequency of aspirin use. In restricting to cases with either high Gleason grade or advanced stage disease, there remained no association with aspirin use.Conclusions: Data from this prospective study with repeated assessments of aspirin use do not support the hypothesis that aspirin use is associated with a lower risk of ERG-positive prostate cancer.Impact: Aspirin use is unlikely to lower the risk of this common molecular subtype of prostate cancer. However, there is emerging data supporting the role of other lifestyle and genetic factors underlying the development of the TMPRSS2:ERG fusion. Cancer Epidemiol Biomarkers Prev; 27(10); 1231-3. ©2018 AACR.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Proteínas de Fusão Oncogênica/metabolismo , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Prognóstico , Estudos Prospectivos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Estados Unidos/epidemiologia
8.
Clin Cancer Res ; 24(23): 5910-5917, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30082473

RESUMO

PURPOSE: Breast and prostate cancer co-occur in families, and women with a family history of prostate cancer are at increased breast cancer risk. Prostate cancer is among the most heritable cancers, but few studies have investigated its association with familial breast cancer. The objective of this study is to investigate the extent to which familial breast or prostate cancer in first-degree relatives increases prostate cancer risk. EXPERIMENTAL DESIGN: A prospective study of 37,002 U.S. men in the Health Professionals Follow-up Study. During the 16-year follow-up to 2012, 4,208 total and 344 lethal cases were diagnosed. Using cause-specific hazards regression, we estimated the multivariable HRs and 95% confidence intervals (CI) for associations between familial breast or prostate cancer and total and lethal prostate cancer. RESULTS: Those with familial breast cancer had a 21% greater risk of prostate cancer overall (95% CI, 1.10-1.34), and a 34% greater risk of lethal disease (HR 1.34; 95% CI, 0.96-1.89). Family history of prostate cancer alone was associated with a 68% increased risk of total disease (95% CI, 1.53-1.83) and a 72% increased risk of lethal disease (95% CI, 1.25-2.38). Men with a family history of both cancers were also at elevated risk. CONCLUSIONS: Our study found that men with a family history of breast or prostate cancer had elevated prostate cancer risks, including risk of lethal disease. These findings have translational relevance for cancer risk prediction in men.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia , Adulto , Idoso , Feminino , Seguimentos , História do Século XX , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/história , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco
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