RESUMO
BACKGROUND: Prostate cancer is ubiquitous in older men; differential screening patterns and variations in biopsy recommendations and acceptance will affect which man is diagnosed and, therefore, evaluation of cancer risk factors. We describe a statistical method to reduce prostate cancer detection bias among African American (nâ¯=â¯3398) and Non-Hispanic White men (nâ¯=â¯22,673) who participated in the Selenium and Vitamin E Cancer Prevention trial (SELECT) and revisit a previously reported association between race, obesity and prostate cancer risk. METHODS: For men with screening values suggesting prostate cancer but in whom biopsy was not performed, the Prostate Cancer Prevention Trial Risk Calculator was used to estimate probability of prostate cancer. Associations of body mass index (BMI) and race with incident prostate cancer were compared for observed versus imputation-enhanced outcomes using incident density ratios. RESULTS: Accounting for differential biopsy assessment, the previously reported positive linear trend between BMI and prostate cancer in African American men was not observed; no BMI association was found among Non-Hispanic White men. CONCLUSIONS: Differential disease classification among men who may be recommended to undergo and then consider whether to accept a prostate biopsy leads to inaccurate identification of prostate cancer risk factors. Imputing a man's prostate cancer status reduces detection bias. Covariate adjustment does not address the problem of outcome misclassification. Cohorts evaluating incident prostate cancer should collect longitudinal screening and biopsy data to adjust for this potential bias.
Assuntos
Biópsia/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Índice de Massa Corporal , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia , População Branca/estatística & dados numéricos , Fatores Etários , Idoso , Biópsia/métodos , Canadá/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Porto Rico/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Encaminhamento e Consulta/estatística & dados numéricos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
IMPORTANCE: African American men have the highest rates of prostate cancer incidence and mortality in the United States. Understanding underlying reasons for this disparity could identify preventive interventions important to African American men. OBJECTIVE: To determine whether the association of obesity with prostate cancer risk differs between African American and non-Hispanic white men and whether obesity modifies the excess risk associated with African American race. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 3398 African American and 22,673 non-Hispanic white men who participated in the Selenium and Vitamin E Cancer Prevention Trial (2001-2011) with present analyses completed in 2014. MAIN OUTCOMES AND MEASURES: Total, low-grade (Gleason score <7), and high-grade (Gleason score ≥7) prostate cancer incidence. RESULTS: With a median (interquartile range) follow-up of 5.6 (1.8) years, there were 270, 148, and 88 cases of total, low-, and high-grade prostate cancers among African American men and a corresponding 1453, 898, and 441 cases in non-Hispanic white men, respectively. Although not associated with risk among non-Hispanic white men, BMI was positively associated with an increase in risk among African American men (BMI, <25 vs ≥35: hazard ratio [HR], 1.49 [95% CI, 0.95, 2.34]; P for trend = .03). Consequently, the risk associated with African American race increased from 28% (HR, 1.28 [95% CI, 0.91-1.80]) among men with BMI less than 25 to 103% (HR, 2.03 [95% CI, 1.38-2.98]) among African American men with BMI at least 35 (P for trend = .03). Body mass index was inversely associated with low-grade prostate cancer risk within non-Hispanic white men (BMI, <25 vs ≥35: HR, 0.80 [95% CI, 0.58-1.09]; P for trend = .02) but positively associated with risk within African American men (BMI, <25 vs ≥35: HR, 2.22 [95% CI, 1.17-4.21]; P for trend = .05). Body mass index was positively associated with risk of high-grade prostate cancer in both non-Hispanic white men (BMI, <25 vs ≥35: HR, 1.33 [95% CI, 0.90-1.97]; P for trend = .01) and African American men, although the increase may be larger within African American men, albeit the racial interaction was not statistically significant (BMI, <25 vs ≥35: HR, 1.81 [95% CI, 0.79-4.11]; P for trend = .02). CONCLUSIONS AND RELEVANCE: Obesity is more strongly associated with increased prostate cancer risk among African American than non-Hispanic white men and reducing obesity among African American men could reduce the racial disparity in cancer incidence. Additional research is needed to elucidate the mechanisms underlying the differential effects of obesity in African American and non-Hispanic white men.
Assuntos
Anticarcinógenos/uso terapêutico , Negro ou Afro-Americano , Disparidades nos Níveis de Saúde , Obesidade/etnologia , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/prevenção & controle , Vitamina E/uso terapêutico , População Branca , Idoso , Índice de Massa Corporal , Canadá/epidemiologia , Distribuição de Qui-Quadrado , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Porto Rico/epidemiologia , Medição de Risco , Fatores de Risco , Selênio/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case-cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status. METHODS: There were 1739 total and 489 high-grade (Gleason 7-10) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided. RESULTS: Toenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium + vitamin E arms) had no effect among men with low selenium status (<60th percentile of toenail selenium) but increased the risk of high-grade PCa among men with higher selenium status by 91% (P = .007). Vitamin E supplementation (alone) had no effect among men with high selenium status (≥40th percentile of toenail selenium) but increased the risks of total, low-grade, and high-grade PCa among men with lower selenium status (63%, P = .02; 46%, P = .09; 111%, P = .008, respectively). CONCLUSIONS: Selenium supplementation did not benefit men with low selenium status but increased the risk of high-grade PCa among men with high selenium status. Vitamin E increased the risk of PCa among men with low selenium status. Men should avoid selenium or vitamin E supplementation at doses that exceed recommended dietary intakes.
Assuntos
Antioxidantes/efeitos adversos , Negro ou Afro-Americano/estatística & dados numéricos , Suplementos Nutricionais/efeitos adversos , Unhas/química , Neoplasias da Próstata/induzido quimicamente , Selênio/efeitos adversos , Vitamina E/efeitos adversos , Idoso , Antioxidantes/administração & dosagem , Antioxidantes/análise , Canadá/epidemiologia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Razão de Chances , Modelos de Riscos Proporcionais , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Porto Rico/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Selênio/administração & dosagem , Selênio/análise , Oligoelementos/efeitos adversos , Estados Unidos/epidemiologia , Vitamina E/administração & dosagem , Vitamina E/análise , Vitaminas/efeitos adversosRESUMO
OBJECTIVES: To evaluate factors affecting the risk of prostate cancer (CaP) and high-grade disease (HGCaP, Gleason score ≥ 7) in a Mexican referral population, with comparison to the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC). METHODS AND MATERIALS: From a retrospective study of 826 patients who underwent prostate biopsy between January 2005 and December 2009 at the Instituto Nacional de Cancerología, Mexico, logistic regression was used to assess the effects of age, prostate-specific antigen (PSA), digital rectal exam (DRE), first-degree family history of CaP, and history of a prior prostate biopsy on CaP and HGCaP, separately. Internal discrimination, goodness-of-fit, and clinical utility of the resulting models were assessed with comparison to the PCPTRC. RESULTS: Rates of both CaP (73.2%) and HGCaP (33.3%) were high among referral patients in this Mexican urology clinic. The PCPTRC generally underestimated the risk of CaP but overestimated the risk of HGCaP. Four factors influencing CaP on biopsy were logPSA, DRE, family history and a prior biopsy history (all P < 0.001). The internal AUC of the logistic model was 0.823 compared with 0.785 of the PCPTRC for CaP (P < 0.001). The same 4 factors were significantly associated with HGCaP as well and the AUC was 0.779 compared with 0.766 of the PCPTRC for HGCaP (P = 0.13). CONCLUSIONS: Lack of screening programs or regular urologic checkups in Mexico imply that men typically first reach specialized clinics with a high cancer risk. This renders diagnostic tools developed on comparatively healthy populations, such as the PCPTRC, of lesser utility. Continued efforts are needed to develop and externally validate new clinical diagnostic tools specific to high-risk referral populations incorporating new biomarkers and more clinical characteristics.
Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Próstata/patologia , Neoplasias da Próstata/patologia , Urologia , Idoso , Biópsia , Exame Retal Digital , Saúde da Família , Humanos , Modelos Logísticos , Masculino , México , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/prevenção & controle , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVES: To perform the first validation study of the finasteride-adjusted Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (finPCPTRC) in a contemporary referral population in Mexico. METHODS: 837 patients referred to the Instituto Nacional de Cancerología, Mexico City, Mexico, between 2005 and 2009 were used to validate the finPCPTRC by examining various measures of discrimination and calibration. Net benefit curve analysis was used to gain insight into the use of the finPCPTRC for clinical decisions. RESULTS: Prostate cancer (PCa) incidence (72.8%) was high in this Mexican referral cohort and 45.7% of men who were diagnosed with PCa had high-grade lesions (HGPCa, Gleason score >6). 1.3% of the patients were taking finasteride. The finPCPTRC was a superior diagnostic tool compared to prostate-specific antigen alone when discriminating patients with PCa from those without PCa (AUC = 0.784 vs. AUC = 0.687, p < 0.001) and when discriminating patients with HGPCa from those without HGPCa (AUC = 0.768 vs. AUC = 0.739, p < 0.001). The finPCPTRC underestimated the risk of PCa but overestimated the risk of HGPCa (both p < 0.001). Compared with other strategies to opt for biopsy, the net benefit would be larger with utilization of the finPCPTRC for patients accepting higher risks of HGPCa. CONCLUSIONS: Rates of biopsy-detectable PCa and HGPCa were high and 1.3% of this referral cohort in Mexico was taking finasteride. The risks of PCa or HGPCa calculated by the finPCPTRC were not well calibrated for this referral Mexican population and new clinical diagnostic tools are needed.
Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Finasterida/uso terapêutico , Programas de Rastreamento/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Encaminhamento e Consulta , Fatores Etários , Idoso , Biópsia , Distribuição de Qui-Quadrado , Exame Retal Digital , Predisposição Genética para Doença , Humanos , Incidência , Modelos Logísticos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Razão de Chances , Linhagem , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
We studied 706 participants of the San Antonio Family Diabetes Study (SAFDS) and 586 male samples from the San Antonio Center for Biomarkers of Risk of Prostate Cancer (SABOR) and used 64 ancestry informative markers to compare admixture proportions between both groups. Existence of population substructure was demonstrated by the excess association of unlinked markers. In the SAFDS sample, ancestral proportions were estimated at 50.2 ± 0.6% European, 46.4 ± 0.6% Native American, and 3.1 ± 0.2% West African. For the SABOR sample, the proportions were 58.9 ± 0.7%, 38.2 ± 0.7%, and 2.9 ± 0.2%, respectively. Additionally, in the SAFDS subjects a highly significant negative correlation was found between individual Native American ancestry and skin reflectance (R(2) = 0.07, P= 0.00006). The correlation was stronger in males than in females but clearly showed that ancestry only accounts for a small percentage of the variation in skin color and, conversely, that skin reflectance is not a robust surrogate for genetic admixture. Furthermore, a substantial difference in substructure is present in the two cohorts of Mexican American subjects from the San Antonio area in Texas, which emphasizes that genetic admixture estimates should be accounted for in association studies, even for geographically related subjects.
Assuntos
Americanos Mexicanos/etnologia , Americanos Mexicanos/genética , Feminino , Ligação Genética , Marcadores Genéticos , Genética Populacional , Humanos , Indígenas Norte-Americanos/genética , Masculino , Linhagem , Pigmentação da Pele/genética , Texas , População Branca/genéticaRESUMO
OBJECTIVES: To determine whether disparities exist in the reporting of lower urinary tract symptoms (LUTS) in non-Hispanic white (NHW), Mexican-American (MA), and African-American (AA) men. METHODS: Data were collected from a prospective, community-based cohort assembled to study risk factors associated with prostate cancer. Measures included demographics, prostate-specific antigen (PSA), body mass index (BMI), and family history of prostate cancer. Lower urinary tract symptom severity was assessed in 2804 men (1485 NHW, 964 MA, 355 AA) without prostate cancer according to the American Urological Association Symptom Index. RESULTS: No significant difference (P = 0.998) was seen in the prevalence of moderate or severe LUTS in NHW (34%), MA (34%), and AA (33%) men. No differences were found in either obstructive or irritative symptoms among the three groups. Age, PSA level, BMI, and family history did not affect symptom severity. CONCLUSIONS: Rates of moderate to severe LUTS symptoms in this cohort were similar to those in other community-based populations of NHW men. Lower rates of moderate or severe symptoms were noted in AA men than previously reported. Mexican-American men had similar degrees of LUTS as the general population, and with their increased risk for diabetes and renal disease, in-depth study of this population is warranted.
Assuntos
Negro ou Afro-Americano , Americanos Mexicanos , Prostatismo/epidemiologia , População Branca , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Prostate cancer continues to be a major health threat, especially among African American men. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), which opened on July 25, 2001, was planned to study possible agents for the prevention of prostate cancer in a population of 32,400 men in the United States, including Puerto Rico, and Canada. SELECT is a phase III randomized, placebo-controlled trial of selenium (200 microg/day from L-selenomethionine) and/or vitamin E (400 IU/day of all rac alpha-tocopheryl acetate) supplementation for a minimum of 7 years (maximum of 12 years) in non-African American men at least 55 years of age and African American men at least 50 years of age. SELECT is a large, simple trial that conforms as closely as possible with community standards of care. This commentary discusses the design problems the SELECT investigators had to resolve in developing the trial, including the role of prostate cancer screening, the best forms and doses of the study agents, and estimation of the event (prostate cancer) rate of men on the placebo arm.