RESUMEN
BACKGROUND: Androgen deprivation therapy (ADT) is an effective palliation treatment in men with advanced prostate cancer (PC). However, ADT has well documented side effects that could alter the patient's health-related quality of life (HRQoL). The current study aims to test whether a genetic stratification could provide better knowledge for optimising ADT options to minimize HRQoL effects. METHODS: A cohort of 206 PC survivors (75 treated with and 131 without ADT) was recruited with written consent to collect patient characteristics, clinical data and HRQoL data related to PC management. The primary outcomes were the percentage scores under each HRQoL subscale assessed using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaires (QLQ-C30 and PR25) and the Depression Anxiety Stress Scales developed by the University of Melbourne, Australia. Genotyping of these men was carried out for the aldo-keto reductase family 1, member C3 (AKR1C3) rs12529 single nucleotide polymorphism (SNP). Analysis of HRQoL scores were carried out against ADT duration and in association with the AKR1C3 rs12529 SNP using the generalised linear model. P-values <0 · 05 were considered significant, and were further tested for restriction with Bonferroni correction. RESULTS: Increase in hormone treatment-related effects were recorded with long-term ADT compared to no ADT. The C and G allele frequencies of the AKR1C3rs12529 SNP were 53·4 % and 46·6 % respectively. Hormone treatment-related symptoms showed an increase with ADT when associated with the AKR1C3 rs12529 G allele. Meanwhile, decreasing trends on cancer-specific symptoms and increased sexual interest were recorded with no ADT when associated with the AKR1C3 rs12529 G allele and reverse trends with the C allele. As higher incidence of cancer-specific symptoms relate to cancer retention it is possible that associated with the C allele there could be higher incidence of unresolved cancers under no ADT options. CONCLUSIONS: If these findings can be reproduced in larger homogeneous cohorts, a genetic stratification based on the AKR1C3 rs12529 SNP, can minimize ADT-related HRQoL effects in PC patients. Our data additionally show that with this stratification it could also be possible to identify men needing ADT for better oncological advantage.
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3-Hidroxiesteroide Deshidrogenasas/genética , Aldehído Reductasa/genética , Antagonistas de Andrógenos/efectos adversos , Hormona Liberadora de Gonadotropina/agonistas , Hidroxiprostaglandina Deshidrogenasas/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Calidad de Vida , Anciano , Anciano de 80 o más Años , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas , Aldo-Ceto Reductasas , Humanos , Masculino , Nueva Zelanda , Neoplasias de la Próstata/enzimologíaRESUMEN
Men with prostate cancer experience many side effects and symptoms that may be improved by a physically active lifestyle. It was hypothesized that older men with prostate cancer who were physically active would report significantly higher levels of quality of life (QOL) as assessed by the WHOQOL-BREF and the WHOQOL-OLD. Of the 348 prostate cancer survivors who were invited to participate in the present postal survey, 137 men returned the questionnaires. Those who were physically active had significantly lower prostate specific antigen (PSA) scores and higher social participation than those insufficiently active. These findings offer some support for the benefits of physical activity (PA) within the prostate cancer population in managing the adverse side effects of their treatments on aspects of their QOL. Future research should more closely examine what types of PA best promote improvements in varying aspects of QOL and psychological well-being for prostate cancer survivors.
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Ejercicio Físico , Neoplasias de la Próstata/psicología , Calidad de Vida , Sobrevivientes/psicología , Anciano , Estudios Transversales , Humanos , Masculino , Antígeno Prostático Específico/sangre , Conducta Sedentaria , Participación Social , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To ascertain whether the current practice at Auckland City Hospital of adding interferon to BCG in patients with high risk or recurrent non-muscle invasive bladder cancer (NMIBC) unable or unwilling to undergo radical cystectomy is effective. SUBJECTS AND METHOD: This study examined all institutional cases where BCG alone had not been effective or tolerated as primary treatment for NMIBC and the next guideline agreed step of radical cystectomy was unable to be performed. We identified all patients unwilling or unable to undergo radical cystectomy due to patient co-morbidities or preference for whom ongoing treatment and care was required and included 45 in the data analysis. Current practice at Auckland City Hospital is adding interferon α-2b to BCG for this population group and all patients that were given this therapy with at least three years of follow up data from diagnosis were included into the study. Patients were either on maintenance BCG or single dosing. Several secondary outcomes were also assessed concurrently to the primary objective. RESULTS: This observational study showed that adding interferon to BCG proved to be an effective therapy for both treatment and salvage therapy in this patient group with 56% of the patients disease (and recurrence) free at the time of audit. 8/45 patients died whilst undergoing treatment with two of these as a direct result of bladder cancer due to disease progression. CONCLUSION: This therapy has improved outcomes at our institution and has a place as a treatment of choice in this difficult to manage patient group.
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Vacuna BCG/administración & dosificación , Factores Inmunológicos/administración & dosificación , Interferón-alfa/administración & dosificación , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Anciano , Auditoría Clínica , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Nueva Zelanda , Proteínas Recombinantes/administración & dosificación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the effects of bariatric surgery on lower urinary tract symptoms (LUTS) in a prospective cohort study. PATIENTS AND METHODS: Patients undergoing bariatric surgery were recruited into the study. LUTS were assessed using the International Prostate Symptoms Score (IPSS) in men and Bristol Female Lower Urinary Tract Symptoms Score Questionnaire (BFLUTS) in women. Serum glucose, insulin and prostate-specific antigen (PSA) levels were recorded; insulin resistance was quantified using the Homeostasis Model Assessment (HOMA-IR) method. Patients were assessed before surgery, and at 6-8 weeks and 1 year after surgery. Weight loss, change in body mass index (BMI), total symptoms score as well as individual symptoms were tested for statistical significance with correction for multiple testing using Bonferroni method. Linear regression analysis was performed with total symptoms score change at 1 year as the outcome variable and BMI, age, total symptoms score before surgery, HOMA-IR, glucose level before surgery, insulin level before surgery, change in insulin level after surgery, weight loss and BMI loss as predictor variables. RESULTS: In all, 86 patients were recruited and 82% completed at least one follow-up after surgery. There was significant weight loss and reduction of BMI after surgery (P < 0.001). At 6 weeks, there was a significant reduction in overall symptom score (P < 0.001) and this improvement was sustained at 1 year. Linear regression analysis showed that total symptoms score at baseline, HOMA-IR, preoperative insulin level and change in insulin level postoperatively were predictive of the change in total symptoms score while the amount of weight loss was not. CONCLUSIONS: The study confirms the improvement in LUTS after weight loss but there is no correlation between the improvement and the time course or degree of weight loss. Rather there is a suggestion that the improvement in symptoms is linked to improvement in insulin resistance seen as a result of both bariatric surgery and weight loss.
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Cirugía Bariátrica , Síntomas del Sistema Urinario Inferior/fisiopatología , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Femenino , Humanos , Insulina/sangre , Síntomas del Sistema Urinario Inferior/sangre , Síntomas del Sistema Urinario Inferior/metabolismo , Síntomas del Sistema Urinario Inferior/cirugía , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/metabolismo , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión , Resultado del Tratamiento , Pérdida de PesoRESUMEN
OBJECTIVE: The primary aim of this study was to examine the perceptions of older men with prostate cancer regarding their quality of life and physical activity post-diagnosis, and the potential benefits and risks associated with being physically active. A secondary aim was to gain some preliminary insight into how these perceptions may differ as a function of androgen deprivation therapy (ADT). METHODS: Two focus groups were conducted, consisting of six ADT and eight non-ADT men, respectively. The probe questions used assessed the link between quality of life and physical activity as well as the benefits and risks associated with physical activity. Data were transcribed verbatim and themes identified using a general inductive thematic approach. RESULTS: The primary themes identified were sexual health, 'plumbing' and non-urogenital side-effects, return to and increased levels of physical activity post-diagnosis, physical health/function and psychological benefits of physical activity as well as over-doing it and age-related risks of excessive physical activity. However, not all themes were present in both the ADT and the non-ADT sub-groups. CONCLUSIONS: These results further highlight the link between physical activity and quality of life in prostate cancer survivors and how they use physical activity as a part of their survivorship process. Of particular interest was how several men on ADT used resistance training to counteract ADT-related side-effects affecting their masculinity. As the evidence for physical activity for prostate cancer survivorship is increasing, cancer clinicians and service providers should consider ways to better assist these men, especially those on ADT become more active.
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Actitud Frente a la Salud , Ejercicio Físico/psicología , Actividad Motora , Neoplasias de la Próstata/psicología , Calidad de Vida , Anciano , Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Estudios de Casos y Controles , Grupos Focales , Humanos , Estilo de Vida , Síntomas del Sistema Urinario Inferior/etiología , Síntomas del Sistema Urinario Inferior/psicología , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/tratamiento farmacológico , Investigación Cualitativa , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Fisiológicas/psicologíaRESUMEN
BACKGROUND: Transrectal ultrasound-guided (TRUS) prostate biopsy is a commonly performed procedure, and fluoroquinolones are the most frequently given prophylactic antimicrobials. In the context of increasing fluoroquinolone resistance, and the international emergence of fluoroquinolone-resistant sequence type 131 (ST131) Escherichia coli, we describe a large series of E. coli bacteremia after TRUS biopsy. METHODS: All male patients admitted with community-onset (CO) E. coli bacteremia from January 2006 through December 2010 were included. Patient characteristics, treatment outcomes, and rates of antimicrobial resistance were compared between patients with TRUS biopsy-related bacteremia and other male patients with CO E. coli bacteremia. Molecular typing was performed on E. coli isolates to determine phylogenetic group. RESULTS: A total of 258 male patients were admitted with CO E. coli bacteremia. Of these, 47 patients (18%) were admitted after TRUS biopsy. Patients who had undergone TRUS biopsy were twice as likely to require intensive care admission (25% vs 12%) and had significantly higher rates of resistance to gentamicin (43%), trimethoprim-sulphamethoxazole (60%), and ciprofloxacin (62%) as well as all 3 agents in combination (19%). Thirty-six percent of post-TRUS biopsy patients did not receive active empirical antibiotic therapy. The ST131 clone accounted for 41% of all E. coli isolates after TRUS biopsy. CONCLUSIONS: E. coli bacteremia can be a life-threatening complication of TRUS biopsy. Infecting strains are frequently multidrug-resistant and resistant to common empirical antibiotic agents. E. coli ST131 is an important cause of sepsis after TRUS biopsy. Further studies should evaluate colonization with fluoroquinolone-resistant E. coli as a risk factor for postbiopsy sepsis.
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Bacteriemia/epidemiología , Biopsia/efectos adversos , Infecciones por Escherichia coli/epidemiología , Escherichia coli/clasificación , Escherichia coli/efectos de los fármacos , Neoplasias de la Próstata/diagnóstico , Ultrasonido Enfocado Transrectal de Alta Intensidad/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/microbiología , Biopsia/métodos , Quimioprevención/métodos , Análisis por Conglomerados , Estudios Transversales , Farmacorresistencia Bacteriana , Escherichia coli/aislamiento & purificación , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Tipificación Molecular , Estudios Retrospectivos , Ultrasonido Enfocado Transrectal de Alta Intensidad/métodos , Adulto JovenRESUMEN
PURPOSE: We investigated whether the RNA assay uRNA® and its derivative Cxbladder® have greater sensitivity for the detection of bladder cancer than cytology, NMP22™ BladderChek™ and NMP22™ ELISA, and whether they are useful in risk stratification. MATERIALS AND METHODS: A total of 485 patients presenting with gross hematuria but without a history of urothelial cancer were recruited prospectively from 11 urology clinics in Australasia. Voided urine samples were obtained before cystoscopy. The sensitivity and specificity of the RNA tests were compared to cytology and the NMP22 assays using cystoscopy as the reference. The ability of Cxbladder to distinguish between low grade, stage Ta urothelial carcinoma and more advanced urothelial carcinoma was also determined. RESULTS: uRNA detected 41 of 66 urothelial carcinoma cases (62.1% sensitivity, 95% CI 49.3-73.8) compared with NMP22 ELISA (50.0%, 95% CI 37.4-62.6), BladderChek (37.9%, 95% CI 26.2-50.7) and cytology (56.1%, 95% CI 43.8-68.3). Cxbladder, which was developed on the study data, detected 82%, including 97% of the high grade tumors and 100% of tumors stage 1 or greater. The cutoffs for uRNA and Cxbladder were prespecified to give a specificity of 85%. The specificity of cytology was 94.5% (95% CI 91.9-96.5), NMP22 ELISA 88.0%, (95% CI 84.6-91.0) and BladderChek 96.4% (95% CI 94.2-98.0). Cxbladder distinguished between low grade Ta tumors and other detected urothelial carcinoma with a sensitivity of 91% and a specificity of 90%. CONCLUSIONS: uRNA and Cxbladder showed improved sensitivity for the detection of urothelial carcinoma compared to the NMP22 assays. Stratification with Cxbladder provides a potential method to prioritize patients for the management of waiting lists.
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Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/orina , Hematuria/orina , ARN/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/orina , Anciano , Carcinoma de Células Transicionales/complicaciones , Carcinoma de Células Transicionales/genética , Femenino , Hematuria/etiología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Estudios Prospectivos , Medición de Riesgo/métodos , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/genética , Orina/citologíaRESUMEN
It is being debated whether prostate-specific antigen (PSA)-based screening effectively reduces prostate cancer mortality. Some of the uncertainty could be related to deficiencies in the age-based PSA cut-off thresholds used in screening. Current study considered 2779 men with prostate cancer and 1606 men without a cancer diagnosis, recruited for various studies in New Zealand, US, and Taiwan. Association of PSA with demographic, lifestyle, clinical characteristics (for cases), and the aldo-keto reductase 1C3 (AKR1C3) rs12529 genetic polymorphisms were analysed using multiple linear regression and univariate modelling. Pooled multivariable analysis of cases showed that PSA was significantly associated with demographic, lifestyle, and clinical data with an interaction between ethnicity and age further modifying the association. Pooled multivariable analysis of controls data also showed that demographic and lifestyle are significantly associated with PSA level. Independent case and control analyses indicated that factors associated with PSA were specific for each cohort. Univariate analyses showed a significant age and PSA correlation among all cases and controls except for the US-European cases while genetic stratification in cases showed variability of correlation. Data suggests that unique PSA cut-off thresholds factorized with demographics, lifestyle and genetics may be more appropriate for prostate cancer screening.
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Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/genética , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios de Cohortes , Demografía , Detección Precoz del Cáncer , Etnicidad , Humanos , Estilo de Vida , Modelos Lineales , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Clasificación del Tumor , Nueva Zelanda/epidemiología , Polimorfismo de Nucleótido Simple , Taiwán/epidemiología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Androgen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers-sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.029 and p = 0.032). Groups contributing to these significant changes were recorded. There were no significant differences in serum DKK-1 levels across the four groups (p = 0.683). In the longitudinal analysis, significant % decreases within groups were seen for DKK-1 [chronic-ADT (- 10.06%, p = 0.0057), former-ADT (- 12.77%, p = 0.0239), and in PCa controls group (- 16.73, p = 0.0022); and OPG levels in chronic ADT (- 8.28%, p = 0.003) and PCa controls group (- 12.82%, p = 0.017)]. However, % changes in sclerostin, DKK-1, and OPG did not differ significantly over 6-months across the evaluated groups. Sclerostin levels showed significant positive correlations with BMD at baseline in the ADT group, while in PCa controls this correlation existed at both baseline and 6-month time points. Sclerostin correlated negatively with testosterone in former ADT users and in PCa controls. Possible prognostic features denoted by parallel increases in sclerostin and BMD are discussed.
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Proteínas Adaptadoras Transductoras de Señales/sangre , Antagonistas de Andrógenos/efectos adversos , Antagonistas de Andrógenos/uso terapéutico , Péptidos y Proteínas de Señalización Intercelular/sangre , Osteoporosis/diagnóstico , Osteoporosis/etiología , Osteoprotegerina/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Biomarcadores/sangre , Densidad Ósea/efectos de los fármacos , Estudios Transversales , Humanos , Estudios Longitudinales , Masculino , Osteoporosis/metabolismoRESUMEN
STUDY TYPE: Symptom prevalence (retrospective cohort) Level of Evidence 2b. OBJECTIVE: To determine the incidence of acute presentation of urinary calculi (UC) in Auckland, New Zealand, during the period 1999-2007, and whether there was any significant seasonal variation. PATIENTS AND METHODS: The details of all UC within the population presenting acutely to public hospitals in Auckland between 1999 and 2007 were collected using clinical coding searches International Classification of Disease 10th revision (Australian Modification) N132 and N20. Climatic variables for the Auckland region were obtained from the National Institute of Water and Atmospheric Research, New Zealand. The mean atmospheric temperature, hours of sunshine and humidity data were calculated monthly for this period. RESULTS: During the study there were 7668 acute presentations of UC in the Auckland region. A Poisson regression model showed that the number of presentations was significantly related to temperature (P < 0.001) and hours of sunshine (P = 0.004) but not humidity (P = 0.14). For each degree increase in temperature the number of presentations increased by 2.8% (95% confidence interval 1.3-4.3%). For each 1-h increase in sunshine, the number of presentations increased by 0.2% (0.06-0.33)%. CONCLUSION: The acute presentation of UC in Auckland, New Zealand, varies significantly with temperature and hours of sunshine. Humidity was not a significant factor.
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Estaciones del Año , Cálculos Urinarios/epidemiología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda/epidemiología , Distribución de Poisson , Adulto JovenRESUMEN
INTRODUCTION: Aldo-keto reductase 1C3 (AKR1C3) is known for multiple functions including its catalytic activity towards producing extra-testicular androgen. The present study is towards understanding interaction between biological, lifestyle and genetic impacts of AKR1C3 and their influence on clinical factors in a prostate cancer (PC) cohort from New Zealand (NZ). METHOD: Characteristics of 516 PC patients were collected from the Auckland Regional Urology Facility, NZ. These men were genotyped for the AKR1C3 rs12529 single nucleotide polymorphism (SNP). The leukocyte AKR1C3 activity was measured in a sub-cohort. Variability of leukocyte AKR1C3 activity between biological, lifestyle and clinical features as well as correlation between biological and clinical features were assessed with and without genetic stratification. RESULTS: The leukocyte AKR1C3 activity was associated with age at diagnosis (0.51 vs 0.34 µM coumberol units for >69y vs ≤69y, P = 0.03); and with anatomic stage/prognostic grouping among the AKR1C3 rs12529 CC genotype carriers (0.50 vs 28 µM coumberol units among low- and high-risk groups respectively, P = 0.02). Significant correlation between leukocyte AKR1C3 activity and age at PC diagnosis was also observed (correlation coefficient 0.20 and P = 0.02). Ever- smoking impacted both age and PSA at PC diagnosis among AKR1C3 rs12529 GG and CG genotype carriers respectively. Age at diagnosis significantly correlated with PSA at diagnosis in the main (correlation coefficient 0.29, and P<0.001) and sub-cohorts (correlation coefficient 0.24, and P = 0.01); and those carrying the AKR1C3 rs12529 CG and GG genotypes in both the main (correlation coefficient 0.30, and P<0.001 and correlation coefficient 0.35, and P<0.001 respectively) and sub-cohorts (correlation coefficient 0.43, and P<0.001 and correlation coefficient 0.39, and P = 0.06 respectively); but not with those carrying the CC genotype. CONCLUSIONS: Age dependent PSA thresholds in PC screening could have been valid only in men carrying the AKR1C3 rs12529 CG and GG genotypes in this NZ cohort.
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Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/sangre , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/genética , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/genética , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios de Cohortes , Genotipo , Humanos , Calicreínas/sangre , Leucocitos/enzimología , Estilo de Vida , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Nueva Zelanda , Polimorfismo de Nucleótido Simple , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/patologíaAsunto(s)
Escherichia coli/enzimología , Escherichia coli/aislamiento & purificación , Recto/microbiología , beta-Lactamasas/metabolismo , Anciano , Antibacterianos/farmacología , ADN Bacteriano/genética , Escherichia coli/genética , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Reacción en Cadena de la Polimerasa , Próstata/diagnóstico por imagen , Análisis de Secuencia de ADN , Ultrasonografía , Ultrasonido Enfocado Transrectal de Alta Intensidad , beta-Lactamasas/genéticaRESUMEN
INTRODUCTION: The prostate-specific antigen (PSA) based prostate cancer (PC) screening is currently being debated. The current assessment is to understand the variability of detecting high-risk PC in a NZ cohort in comparison to a US cohort with better PSA screening facilities. Aldo-keto reductase 1C3 (AKR1C3) is known for multiple functions with a potential to regulate subsequent PSA levels. Therefore, we wish to understand the influence of tobacco smoking and the AKR1C3 rs12529 gene polymorphism in this variability. METHOD: NZ cohort (n = 376) consisted of 94% Caucasians while the US cohort consisted of African Americans (AA), n = 202, and European Americans (EA), n = 232. PSA level, PC grade and stage at diagnosis were collected from hospital databases for assigning high-risk PC status. Tobacco smoking status and the AKR1C3 rs12529 SNP genotype were considered as confounding variables. Variation of the cumulative % high-risk PC (outcome variable) with increasing PSA intervals (exposure factor) was compared between the cohorts using the Kolmogorov-Smirnov test. Comparisons were carried out with and without stratifications made using confounding variables. RESULTS: NZ cohort has been diagnosed at a significantly higher mean age (66.67± (8.08) y) compared to both AA (62.65±8.17y) and EA (64.83+8.56y); median PSA (NZ 8.90ng/ml compared to AA 6.86ng/ml and EA 5.80ng/ml); and Gleason sum (NZ (7) compared EA (6)) (p<0.05). The cumulative % high-risk PC detection shows NZ cohort with a significantly lower diagnosis rates at PSA levels between >6 - <10ng/ml compared to both US groups (p<0.05). These were further compounded significantly by smoking status and genetics. CONCLUSIONS: High-risk PCs recorded at higher PSA levels in NZ could be due to factors including lower levels of PSA screening and subsequent specialist referrals for biopsies. These consequences could be pronounced among NZ ever smokers carrying the AKR1C3 rs12529 G alleles making them a group that requires increased PSA screening attention.
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Adenocarcinoma/genética , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/genética , Detección Precoz del Cáncer , Variación Genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Fumar/metabolismo , Activación Metabólica/genética , Adenocarcinoma/sangre , Adenocarcinoma/enzimología , Adenocarcinoma/etnología , Negro o Afroamericano , Anciano , Diagnóstico Tardío , Europa (Continente)/etnología , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda , Antígeno Prostático Específico/biosíntesis , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/etnología , Riesgo , Fumar/epidemiología , Fumar/genética , Determinantes Sociales de la Salud , Estados Unidos , Población BlancaRESUMEN
BACKGROUND: Aldo-keto reductase 1C3 (AKR1C3) is an important oxidoreductase with multiple substrates, that are involved in producing extra-testicular androgens. Its activity is influenced by environmental exposures, as well as by genetic variants. These genetic variants could therefore produce variable testosterone levels and subsequent androgen receptor (AR) activation. This could lead to differential downstream production of the prostate-specific antigen (PSA). As PSA level is used for clinical evaluation of the prostate, these variations could impact prostate cancer (PC) diagnosis, as well as PC management outcomes. This review brings together information with regards to key functions of this enzyme, its relevance in PC, its transcriptional regulation, clinical aspects associated with genetics, differential regulation in cancer and cancer progression, and the types of AKR1C3 inhibitors with future therapeutic value. CONCLUSION: Based on these discussions, hypotheses are forwarded for future applicability of this enzyme and its genetic variants in transformational medical practices in PC. Options for the use of personalised AKR1C3 inhibitor drugs for late stage PC are also discussed.
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Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/genética , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/metabolismo , Neoplasias de la Próstata/patología , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/antagonistas & inhibidores , Andrógenos/metabolismo , Resistencia a Antineoplásicos , Inhibidores Enzimáticos/farmacología , Regulación Enzimológica de la Expresión Génica , Humanos , Masculino , Terapia Molecular Dirigida/métodos , Polimorfismo Genético , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genéticaRESUMEN
INTRODUCTION: Reduction in bone mineral density (BMD) is a common side effect of androgen deprivation therapy (ADT). We aimed to examine the cross-sectional and longitudinal variation in BMD and associated bone markers in patients with nonmetastatic prostate cancer (PCa) managed with and without ADT. METHODS: Bone mineral density of the total body, lumbar spine, femoral neck, ultradistal forearm, and one-third distal radius was measured in 88 patients with PCa without bone metastases at baseline and at 6 months. Patients were categorized into 4 groups: (1) acute ADT (≤6 months), (2) chronic ADT (>6 months), (3) former ADT, and (4) no ADT (controls). Serum levels of bone metabolism markers, procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX), were also measured. RESULTS: In the cross-sectional analysis, men receiving chronic ADT had significantly lower total body BMD as compared with former ADT users and men with no ADT. In longitudinal analysis, a significant reduction in ultradistal forearm BMD was observed in both acute and chronic ADT users after 6 months (4.08% and 2.7%, P = .012 and .026, respectively). A significant reduction in total body BMD was observed in acute ADT users (2.99%, P = .032). Former ADT users had a significant increase in both lumbar spine and femoral neck BMD (2.84% and 1.59%, P = .008 and .002, respectively). The changes in BMD were not significantly different between acute and chronic ADT users. In the cross-sectional analysis, higher levels of PINP and CTX were observed in acute and chronic ADT users than former ADT users or PCa controls. In longitudinal analysis, the level of serum PINP and CTX did not change significantly from baseline to 6 months in acute, chronic, and former ADT users, or PCa controls, and the percentage change did not differ among the 4 groups. CONCLUSIONS: Men on acute ADT had a similar rate of bone loss to men on chronic ADT. Reversibility in ADT-induced bone loss was observed in those who discontinued ADT. Serum levels of PINP and CTX were higher in acute and chronic ADT users and levels returned to the range of PCa controls when treatment was withdrawn.
RESUMEN
Prostate cancer is an important health burden to the healthcare system of any country. However, with the current prostate-specific antigen biomarker having low predictive value even for diagnostic purposes, the challenge is still open to tackle this chronic disease. There have been a number of studies which have indicated and encouraged a multi-directional approach to combat this disease. We have been carrying out a multi-directional approach in order to identify certain New Zealand-specific factors which may be drivers for this cancer and its aggressive forms. These will be explained in further detail in this research letter.
Asunto(s)
Neoplasias de la Próstata , Biomarcadores de Tumor , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Nueva Zelanda/epidemiología , Antígeno Prostático EspecíficoRESUMEN
Prostate cancer is one of the most significant health concerns for men worldwide. Numerous researchers carrying out molecular diagnostics have indicated that genetic interactions with biological and behavioral factors play an important role in the overall risk and prognosis of this disease. Single nucleotide polymorphisms (SNPs) are increasingly becoming strong biomarker candidates to identify susceptibility to prostate cancer. We carried out a gene × environment interaction analysis linked to aggressive and non-aggressive prostate cancer (PCa) with a number of SNPs. By using this method, we identified the susceptible alleles in a New Zealand population, and examined the interaction with environmental factors. We have identified a number of SNPs that have risk associations both with and without environmental interaction. The results indicate that certain SNPs are associated with disease vulnerability based on behavioral factors. The list of genes with SNPs identified as being associated with the risk of PCa in a New Zealand population is provided in the graphical abstract.
Asunto(s)
Ambiente , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Vigilancia de la Población , Neoplasias de la Próstata/etiología , Neoplasias de la Próstata/patología , Alelos , Estudios de Casos y Controles , Estudios de Asociación Genética , Genotipo , Humanos , Estilo de Vida , Masculino , Clasificación del Tumor , Nueva Zelanda/epidemiología , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Pronóstico , Neoplasias de la Próstata/mortalidad , Medición de Riesgo , Factores de RiesgoRESUMEN
Background. Prostate cancer makes up approximately 15% of all cancers diagnosed in men in developed nations and approximately 4% of cases in developing nations. Although it is clear that prostate cancer has a genetic component and single nucleotide polymorphisms (SNPs) can contribute to prostate cancer risk, detecting associations is difficult in multi-factorial diseases, as environmental and lifestyle factors also play a role. In this study, specific clinical characteristics, environmental factors and genetic risk factors were assessed for interaction with prostate cancer. Methods. A total of 489 prostate cancer cases and 427 healthy controls were genotyped for SNPs found on chromosome 8q24 and a genetic risk score was calculated. In addition the SNPs were tested for an association with a number of clinical and environmental factors. Results. Age and tobacco use were positively associated, whilst alcohol consumption was negatively associated with prostate cancer risk. The following SNPs found on chromosome 8q24 were statistically significantly associated with prostate cancer: rs10086908, rs16901979; rs1447295and rs4242382. No association between Gleason score and smoking status, or between Gleason score and genotype were detected. Conclusion. A genetic risk score was calculated based on the 15 SNPs tested and found to be significantly associated with prostate cancer risk. Smoking significantly contributed to the risk of developing prostate cancer, and this risk was further increased by the presence of four SNPs in the 8q24 chromosomal region.
RESUMEN
The essential micronutrient, selenium, is at low levels in the New Zealand diet. Selenium is a component of a number of proteins involved in the maintenance of genomic stability, and recommended daily allowances (RDA) are set on saturation levels for glutathione peroxidase (GPx), a key enzyme in surveillance against oxidative stress. It has been assumed but not proven that this level will be adequate for other key selenoenzymes. The "Negative Biopsy Trial" identifies a group of New Zealand individuals at high risk of prostate cancer, whose serum selenium levels will be monitored and who will be supplemented with a yeast-based tablet, with or without selenium, over an extended time. Access to patients on this trial provides the opportunity to ask the more generic question as to whether selenium levels in this population are adequate to maintain genomic stability. The single cell gel electrophoresis (comet) assay was used to study DNA damage in blood leukocytes harvested from these volunteers. Average serum selenium levels before randomization was 97.8 +/- 16.6 ng/ml, low by international standards. For the half of the population below this mean value, lower serum selenium levels showed a statistically significant inverse relationship (P = 0.02) with overall accumulated DNA damage. Although other interpretations cannot be excluded, the data suggest that the selenium intake in half of this population is marginal for adequate repair of DNA damage, increasing susceptibility to cancer and other degenerative diseases. It also raises the question as to whether glutathione peroxidase saturation levels are appropriate indicators of the optimal selenium levels for a given population.