Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
PLoS One ; 15(8): e0237430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841307

RESUMO

BACKGROUND & AIMS: Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans. METHODS: MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts. RESULTS: Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis. CONCLUSIONS: We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.


Assuntos
Alanina Transaminase/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , 17-Hidroxiesteroide Desidrogenases/genética , Abdome/diagnóstico por imagem , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Alanina Transaminase/genética , Registros Eletrônicos de Saúde , Feminino , Loci Gênicos , Predisposição Genética para Doença , Variação Genética , Humanos , Lipase/genética , Fígado/patologia , Lisofosfolipase/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etnologia , Hepatopatia Gordurosa não Alcoólica/genética , Fenótipo , Fatores de Risco , Veteranos
3.
Am J Hum Genet ; 106(4): 535-548, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32243820

RESUMO

The Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect biosamples with consent from at least one million veterans. Presently, blood samples have been collected from over 800,000 enrolled participants. The size and diversity of the MVP cohort, as well as the availability of extensive VA electronic health records, make it a promising resource for precision medicine. MVP is conducting array-based genotyping to provide a genome-wide scan of the entire cohort, in parallel with whole-genome sequencing, methylation, and other 'omics assays. Here, we present the design and performance of the MVP 1.0 custom Axiom array, which was designed and developed as a single assay to be used across the multi-ethnic MVP cohort. A unified genetic quality-control analysis was developed and conducted on an initial tranche of 485,856 individuals, leading to a high-quality dataset of 459,777 unique individuals. 668,418 genetic markers passed quality control and showed high-quality genotypes not only on common variants but also on rare variants. We confirmed that, with non-European individuals making up nearly 30%, MVP's substantial ancestral diversity surpasses that of other large biobanks. We also demonstrated the quality of the MVP dataset by replicating established genetic associations with height in European Americans and African Americans ancestries. This current dataset has been made available to approved MVP researchers for genome-wide association studies and other downstream analyses. Further data releases will be available for analysis as recruitment at the VA continues and the cohort expands both in size and diversity.


Assuntos
Grupos Étnicos/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Marcadores Genéticos/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Medicina de Precisão/métodos , Controle de Qualidade , Veteranos , Sequenciamento Completo do Genoma/métodos
4.
Int J Cancer ; 147(3): 675-685, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31677159

RESUMO

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type-hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that include data from 1,167,244 individuals (PLC n = 2,208, HCC n = 1,154, ICC n = 335). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR = 1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR = 1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5 to <25 kg/m2 ; HR = 1.14, 95%CI: 1.07-1.21). Hip circumference, per 5 cm increase, was associated with a 9% increased PLC risk (HR = 1.09, 95%CI: 1.06-1.12), but no association remained after adjustment for waist circumference (HR = 0.99, 95%CI: 0.94-1.03). HCC and ICC results were similar. These findings suggest that excess abdominal size is associated with an increased risk of liver cancer, even among individuals considered to have a normal BMI. However, excess gluteofemoral size alone confers no increased risk. Our findings extend prior analyses, which found an association between excess adiposity and risk of liver cancer, by disentangling the separate effects of excess abdominal and gluteofemoral size through utilization of both waist and hip circumference measurements.

5.
Eur J Nutr ; 59(3): 935-940, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30919083

RESUMO

PURPOSE: Atrial fibrillation (AF) is a frequently encountered cardiac arrhythmia in clinical practice. While fried food consumption is common in United States, little is known about the association between fried food consumption and incident AF. METHODS: We prospectively examined the association of fried food consumption with incident AF in 18,941 US male physicians. Fried food consumption was assessed via a self-administered food frequency questionnaire. Incident AF was ascertained through yearly follow-up questionnaires. Cox regression was used to estimate relative risks of AF. RESULTS: The average age at baseline was 66 ± 9 years. During a mean follow up of 9.0 ± 3.0 years, 2099 new cases of AF occurred. Using < 1/week of fried food consumption as the reference group, multivariable adjusted hazard ratios ( 95% confidence interval) for AF were 1.07 (0.97, 1.18) and 1.03 (0.91, 1.17), for people reporting an average fried food consumption of 1-3/week and ≥ 4/week, respectively, p linear trend 0.4. In a secondary analysis, the results did not change after exclusion of participants with prevalent coronary heart disease or congestive heart failure. Lastly, the source of fried food (away from home or at home) did not influence the relation of fried food with AF risk. CONCLUSIONS: In conclusion, our study does not provide evidence for an association between fried food consumption and incident AF among US male physicians.

6.
Eur J Nutr ; 57(8): 2937-2942, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29094199

RESUMO

BACKGROUND AND AIMS: Although the association between monounsaturated fatty acids (MUFA) and risk factors for heart failure (HF) has been reported, it is unclear whether oleic acid, the predominant MUFA in olive oil, plays a role in the development of HF. Consequently, we sought to examine the relation of plasma phospholipid oleic acid with HF in a male cohort. In a secondary analysis, we examined the relation of the ratio of plasma monounsaturated-to-saturated fatty acids (MUFA: SFA) with HF. METHODS: This prospective nested case-control study was based on 788 incident HF cases and 788 controls from the Physicians' Health Study. Plasma phospholipid fatty acids were measured using gas chromatography and incident HF was self-reported via annual follow-up questionnaires and validated in a subsample using medical records. RESULTS: The mean age was 58.7 years at blood collection. In a conditional logistic regression, multivariable adjusted-odds ratios (95% confidence interval) for HF across consecutive quartiles of oleic acid were 1.0 (reference), 1.10 (0.79-1.54), 1.02 (0.72-1.44), and 1.05 (0.72-1.54). For MUFA:SFA ratio, corresponding odds ratios (95% CI) for HF were 1.0 (ref), 1.12 (0.80-1.58), 1.19 (0.84-1.68), and 0.97 (0.66-1.42). CONCLUSIONS: Our data do not lend support to an association between plasma phospholipid oleic acid or MUFA: SFA ratio and the risk of HF. These results warrant confirmation in the general population including women and other ethnic groups.


Assuntos
Insuficiência Cardíaca/sangue , Ácido Oleico/sangue , Fosfolipídeos/sangue , Estudos de Casos e Controles , Estudos de Coortes , Ácidos Graxos Monoinsaturados/sangue , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Azeite de Oliva/administração & dosagem , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Inquéritos e Questionários
7.
Arch Gerontol Geriatr ; 71: 21-27, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28242579

RESUMO

BACKGROUND: As the population ages it is important to identify frailty, a powerful predictor of morbidity and mortality, and often an important unmeasured confounder. We sought to develop a frailty index in the Physician's Health Study (PHS) and estimate the association with mortality. METHODS: Prospective cohort study. Annual questionnaire assessed mood, function and health status. Two frailty scores were compared - cumulative deficit frailty index (PHS FI) and modified Study of Osteoporotic Fracture (mSOF) frailty score. Endpoints committee confirmed mortality. RESULTS: 12,180 male physicians ≥60 years were analyzed. Mean(SD) follow-up was 10(3) years, 2168 deaths occurred. PHS FI identified 4412 (36%) physicians robust, 5305 (44%) pre-frail, and 2463 (20%) frail, while mSOF identified 7323 (61%) robust, 3505 (29%) pre-frail and 1215 (10%) frail. Age-standardized rate of death was lower among subjects identified as robust using the PHS FI, 11/1000 person-years (PY) (95% Confidence Interval (CI): 9.5-11.9) compared to 14/1000PY (95% CI: 13.5-15.4) using mSOF [P-difference <0.001]. In the prefrail group, death rates were 16/1000PY in PHS FI and 21/1000PY in mSOF, [P-difference <0.001]. There was no difference in age-adjusted mortality rates in the frail group according to each definition (35 vs 33/1000PY). Survival analysis showed an increased risk of mortality in each frailty category using either definition, (log-rank p<0.001). CONCLUSION: The PHS FI outperformed mSOF in identifying risk of death particularly in robust and pre-frail categories. Similar indices can be created in existing datasets to identify frail individuals and where appropriate account for frailty, an often unmeasured confounder.


Assuntos
Fragilidade , Idoso , Idoso de 80 Anos ou mais , Fragilidade/mortalidade , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos
8.
Am J Cardiol ; 116(4): 563-6, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26076989

RESUMO

Chocolate consumption has been shown to protect against various cardiovascular end points; however, little is known about the association between chocolate consumption and incident atrial fibrillation (AF). Therefore, we prospectively examined the association between chocolate consumption and incident AF in a cohort of 18,819 US male physicians. Chocolate consumption was ascertained from 1999 to 2002 through a self-administered food frequency questionnaire. Incident AF was ascertained through yearly follow-up questionnaires. Cox regression was used to estimate relative risks of AF. The average age at baseline was 66 years (±9.1). During a mean follow-up of 9.0 years (±3.0), 2,092 cases of AF occurred. Using <1 per month of chocolate consumption as the reference group, multivariable adjusted hazard ratios (95% confidence interval) for AF were 1.04 (0.93 to 1.18), 1.10 (0.96 to 1.25), 1.14 (0.99 to 1.31), and 1.05 (0.89 to 1.25) for chocolate intake of 1 to 3 per month and 1, 2 to 4, and ≥5 per week (p for trend 0.25), respectively. In a secondary analysis, there was no evidence of effect modification by adiposity (p interaction = 0.71) or age (p interaction = 0.26). In conclusion, our data did not support an association between chocolate consumption and risk of AF in US male physicians.


Assuntos
Fibrilação Atrial/epidemiologia , Cacau , Dieta , Idoso , Aspirina/uso terapêutico , Fibrilação Atrial/diagnóstico , Estudos de Coortes , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/prevenção & controle , Médicos , Inibidores da Agregação de Plaquetas/uso terapêutico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários , Vitaminas/uso terapêutico , beta Caroteno/uso terapêutico
9.
Zhongguo Fei Ai Za Zhi ; 17(9): 649-55, 2014 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-25248705

RESUMO

BACKGROUND: Lung cancer is the most common cancer and cancer related cause of death worldwide. However, the association between sleep duration and incident lung cancer has not been investigated in a prospective cohort study. METHODS: We prospectively examined the association between sleep duration and incident lung cancer in a cohort of 21,026 United States (US) male physicians. Self-reported sleep duration was ascertained during 2002 annual follow-up questionnaire. Incident lung cancer was ascertained through yearly follow-up questionnaires. Cox regression was used to estimate relative risk of incident lung cancer. RESULTS: The average age at baseline was 68.3±8.8 yr. During a mean follow up of 7.5 (±2.2) yr, 150 cases of lung cancer occurred. Using 7 h of sleep as the reference group, multivariable adjusted hazard ratios (95%CI) for lung cancer were 1.18 (0.77-1.82), 1.0 (ref), and 0.97 (0.67-1.41) from lowest to the highest category of sleep duration (P for quadratic trend 0.697), respectively. In a secondary analysis, smoking status did not modify the sleep duration-lung cancer association (P=0.78). There was no evidence for an interaction between sleep duration and sleep apnea on the risk of lung cancer either (P=0.65). CONCLUSIONS: Our data failed to show a higher risk of lung cancer in association with altered sleep duration among US male physicians.


Assuntos
Saúde , Neoplasias Pulmonares/epidemiologia , Médicos/estatística & dados numéricos , Sono , Idoso , Estudos de Coortes , Humanos , Neoplasias Pulmonares/fisiopatologia , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Fatores de Tempo , Estados Unidos/epidemiologia
10.
Curr Atheroscler Rep ; 16(11): 450, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25214423

RESUMO

Cardiovascular disease (CVD) is the leading cause of death in the USA. A diet enriched with n-3 fatty acids (FA) has been reported to play an important role in preventing the development of CVD. Prior studies have demonstrated beneficial effects of n-3 FA on hypertriglyceridemia, blood pressure, inflammation, endothelial function, and platelet function. However, data on the relation of n-3 FA consumption with CVD risk remain inconsistent. This paper reviews current evidence on the effects of n-3 FA on CVD, CVD risk factors, and potential biologic mechanisms. Last, we discuss major limitations of currently available data and future directions in the field.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Dieta , Ácidos Graxos Ômega-3/uso terapêutico , Doenças Cardiovasculares/metabolismo , Ensaios Clínicos como Assunto , Ácidos Graxos Ômega-3/metabolismo , Humanos , Fatores de Risco
11.
Am J Cardiol ; 110(4): 539-44, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22579341

RESUMO

Although previous studies have suggested associations between plasma palmitoleic acid and coronary heart disease (CHD) risk factors, including blood pressure, inflammation, and insulin resistance, little is known about the relation of palmitoleic acid and CHD. This ancillary study of the Physicians' Health Study was designed to examine whether red blood cell (RBC) membrane cis-palmitoleic acid and cis-vaccenic acid-2 fatty acids that can be synthesized endogenously-are associated with CHD risk. We used a risk set sampling method to prospectively select 1,000 incident CHD events and 1,000 matched controls. RBC membrane fatty acids were measured using gas chromatography. The CHD cases were ascertained using an annual follow-up questionnaire and validated by an End Point Committee through a review of the medical records. In a conditional logistic regression analysis adjusting for demographics, anthropometric, lifestyle factors, and co-morbidity, the odds ratios and 95% confidence intervals (CIs) for CHD were 1.0 (referent), 1.29 (95% CI 0.95 to 1.75), 1.08 (95% CI 0.78 to 1.51), 1.25 (95% CI 0.90 to 1.75), and 1.48 (95% CI 1.03 to 2.14) across consecutive quintiles of RBC membrane cis-palmitoleic acid (p for trend = 0.041). The odds ratio associated with each SD higher RBC membrane cis-palmitoleic acid level was 1.19 (95% CI 1.06 to 1.35) in a multivariate-adjusted model. Finally, RBC membrane cis-vaccenic acid was inversely associated with CHD risk (odds ratio 0.79, 95% CI 0.69 to 0.91, per SD increase). In conclusion, our data showed a positive association between RBC membrane cis-palmitoleic acid and CHD risk in male physicians. Furthermore, RBC membrane cis-vaccenic acid was inversely related to CHD.


Assuntos
Doença das Coronárias/metabolismo , Membrana Eritrocítica/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Ácidos Oleicos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Doença das Coronárias/sangue , Doença das Coronárias/complicações , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Inquéritos e Questionários , Estados Unidos
12.
Carcinogenesis ; 31(3): 455-61, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19965896

RESUMO

Genes involved in the inflammation pathway have been associated with cancer risk. Genetic variants in the interleukin-6 (IL6) and prostaglandin-endoperoxide synthase-2 (PTGS2, encoding for the COX-2 enzyme) genes, in particular, have been related to several cancer types, including breast and prostate cancers. We conducted a study within the Breast and Prostate Cancer Cohort Consortium to examine the association between IL6 and PTGS2 polymorphisms and breast and prostate cancer risk. Twenty-seven polymorphisms, selected by pairwise tagging, were genotyped on 6292 breast cancer cases and 8135 matched controls and 8008 prostate cancer cases and 8604 matched controls. The large sample sizes and comprehensive single nucleotide polymorphism tagging in this study gave us excellent power to detect modest effects for common variants. After adjustment for multiple testing, none of the associations examined remained statistically significant at P = 0.01. In analyses not adjusted for multiple testing, one IL6 polymorphism (rs6949149) was marginally associated with breast cancer risk (TT versus GG, odds ratios (OR): 1.32; 99% confidence intervals (CI): 1.00-1.74, P(trend) = 0.003) and two were marginally associated with prostate cancer risk (rs6969502-AA versus rs6969502-GG, OR: 0.87, 99% CI: 0.75-1.02; P(trend) = 0.002 and rs7805828-AA versus rs7805828-GG, OR: 1.11, 99% CI: 0.99-1.26; P(trend) = 0.007). An increase in breast cancer risk was observed for the PTGS2 polymorphism rs7550380 (TT versus GG, OR: 1.38, 99% CI: 1.04-1.83). No association was observed between PTGS2 polymorphisms and prostate cancer risk. In conclusion, common genetic variation in these two genes might play at best a limited role in breast and prostate cancers.


Assuntos
Adenocarcinoma/genética , Neoplasias da Mama/genética , Ciclo-Oxigenase 2/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Adenocarcinoma/epidemiologia , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Doença Crônica , Estudos de Coortes , Grupos Étnicos/genética , Grupos Étnicos/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Risco , Estados Unidos/epidemiologia
13.
Int J Environ Res Public Health ; 6(2): 635-42, 2009 02.
Artigo em Inglês | MEDLINE | ID: mdl-19440406

RESUMO

Cigarette use is a known risk factor for the development of coronary artery disease (CAD) as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR) and 95% confidence intervals (CI) of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively), as did the diagnosis of diabetes (2.40 to 7.79%). Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively), however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol at both time points if they were current smokers (1982 OR 1.44, CI 1.4-1.7; 1997 OR 1.71, CI 1.48-1.97), past smokers (1982 OR 1.12, CI 1.05-1.18; 1997 OR 1.13, CI 1.06-1.20), overweight (BMI 25 kg/m2) or sedentary. In addition, physicians who never quit smoking were likely to be unaware of their cholesterol throughout the study (OR 1.42, CI 1.21-1.67). Cholesterol awareness in general and among those with CAD risk factors improved after 14-years of follow-up. However, the likelihood of being unaware was greater among smokers at both time points. Therefore, smokers do not appear to take advantage of other preventive strategies that would minimize their risk of developing CAD.


Assuntos
Conscientização , Colesterol/sangue , Médicos , Fumar , Humanos , Inquéritos e Questionários
14.
Int J Angiol ; 17(2): 78-82, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-22477392

RESUMO

BACKGROUND: The use of diagnostic imaging in the United States continues to increase, while investigations of the clinical implications following testing are lacking. The objectives of the present study are to describe the practice patterns and clinical outcomes that follow lower extremity diagnostic imaging. This is a retrospective cohort study with six years of data (1999 to 2004). METHODS: The sources of data for the present study were Veterans Affairs Hospital administrative and clinical databases. The study population included 19,209 American veterans who had either contrast-enhanced magnetic resonance angiography (MRA) or digital subtraction angiography (DSA) for the assessment of peripheral artery occlusive disease. Descriptive statistics of the characteristics were provided, as well as adjusted ORs for having interventions or complications following an imaging procedure. RESULTS: The number of patients initially imaged with a contrast-enhanced MRA increased from 1999 to 2004, while those imaged with DSA decreased. The overall imaging rate remained relatively constant. In the multivariate model adjusted for the risk of complications within 30 days of the initial imaging procedure, the risk of complications following DSA increased 2.29-fold (95% CI 1.60 to 3.30). More patients had an intervention following DSA (DSA 41% versus MRA 23%, P<0.0001) but were also twice as likely to have an intervention with an amputation (adjusted OR 2.36, 95% CI 1.79 to 3.12). CONCLUSIONS: The present study illustrates the need for prospective evaluation of diagnostic imaging to determine how best to employ screening strategies that will optimize diagnostic imaging and treatment in patients diagnosed with peripheral artery occlusive disease.

15.
Cancer Res ; 67(7): 2951-6, 2007 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-17409400

RESUMO

Two recent studies independently identified polymorphisms in the 8q24 region, including a single nucleotide polymorphism (rs1447295), strongly associated with prostate cancer risk. Here, we replicate the overall association in a large nested case-control study from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium using 6,637 prostate cancer cases and 7,361 matched controls. We also examine whether this polymorphism is associated with breast cancer among 2,604 Caucasian breast cancer cases and 3,118 matched controls. The rs1447295 marker was strongly associated with prostate cancer among Caucasians (P = 1.23 x 10(-13)). When we exclude the Multiethnic Cohort samples, previously reported by Freedman et al., the association remains highly significant (P = 8.64 x 10(-13)). Compared with wild-type homozygotes, carriers with one copy of the minor allele had an OR(AC) = 1.34 (99% confidence intervals, 1.19-1.50) and carriers with two copies of the minor allele had an OR(AA) = 1.86 (99% confidence intervals, 1.30-2.67). Among African Americans, the genotype association was statistically significant in men diagnosed with prostate cancer at an early age (P = 0.011) and nonsignificant for those diagnosed at a later age (P = 0.924). This difference in risk by age at diagnosis was not present among Caucasians. We found no statistically significant difference in risk when tumors were classified by Gleason score, stage, or mortality. We found no association between rs1447295 and breast cancer risk (P = 0.590). Although the gene responsible has yet to be identified, the validation of this marker in this large sample of prostate cancer cases leaves little room for the possibility of a false-positive result.


Assuntos
Neoplasias da Mama/genética , Cromossomos Humanos Par 8/genética , Neoplasias da Próstata/genética , Grupo com Ancestrais do Continente Africano , Idoso , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/patologia
16.
PLoS Genet ; 1(5): e68, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16311626

RESUMO

Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17beta-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Delta5-androsterone-3beta,17beta-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites.


Assuntos
17-Hidroxiesteroide Desidrogenases/genética , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Neoplasias da Próstata/genética , Idoso , Variação Genética , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/etnologia , Risco , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...