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1.
Prostate ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33599307

RESUMO

BACKGROUND: Mutations of the BRCA2 gene are the most frequent alterations found in germline DNA from men with prostate cancer (PrCa), but clinical parameters that could better orientate for BRCA2 mutation screening need to be established. METHODS: Germline DNA from 325 PrCa patients (median age at diagnosis: 57 years old) was screened for BRCA2 mutation. The mutation frequency was compared between three subgroups: patients with an age at diagnosis at 55 years old and under (Group I); a personal or family history of breast, uterine or ovarian cancer (Group II); or a metastatic disease (Group III). Frequency of BRCA2 mutations was established for each combination of phenotypes, and compared between patients meeting or not the criteria for each subgroup using Fisher's exact test. Mutual information, direct effect, elasticity and contribution to the mutational status of each phenotype, taking into account overlap between subgroups, were also estimated using Bayesian algorithms. RESULTS: The proportion of BRCA2 mutation was 5.9% in Group I, 10.9% in Group II and 6.9% in Group III. The frequency of BRCA2 mutation was significantly higher among patients of Group II (p = .006), and reached 15.6% among patients of this group who presented a metastatic disease. Mutual information, direct effect, elasticity and contribution to the mutational status were the highest for phenotype II. Fifteen (71.4%) of the 21 BRCA2 mutation carriers had an aggressive form of the disease. Four (19%) of them died from PrCa after a median follow-up duration of 64.5 months. CONCLUSIONS: Our results showed that a higher frequency of BRCA2 mutation carriers is observed, not only among PrCa patients with young onset or a metastatic disease, but also with a personal or a familial history of breast cancer.

2.
BMC Cancer ; 21(1): 61, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446131

RESUMO

BACKGROUND: Prostate cancer among black men is known to have specific molecular characteristics, especially the androgen receptor or enzymes related to the androgen metabolism. These targets are keys to the action of new hormonal therapies. Nevertheless, literature has a lack of data regarding black men. We aimed to gather the available literature data on new hormonal therapies among black populations. METHODS: We conducted a literature review from the PubMed / MEDLINE database until October 2020. All clinical studies of new hormonal therapies and black populations, regardless of methodology, were included. RESULTS: Four studies provided data on new hormonal therapies in black populations. Three studies reported a PSA decline in black patients treated with Abiraterone, higher in black men than in white men. Overall survival also appears to be higher in black patients treated with Abiraterone only or first. CONCLUSION: Few articles have evaluated the effectiveness and safety of use of these treatments among black populations. The first results seem to show that Abiraterone can provide a benefit in overall survival in black populations. Prospective studies are needed to answer these questions in the future.

3.
Int J Cancer ; 148(1): 99-105, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32930425

RESUMO

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.

4.
Eur Urol ; 78(3): 316-320, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32409115

RESUMO

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.

5.
World J Urol ; 38(6): 1493-1499, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31485740

RESUMO

PURPOSE: The Grade Group (GG) classification is recommended by guidelines as a reliable prognostic factor of prostate cancer. However, most studies have been performed on the Caucasian population. Our objective was to validate GG classification as a safe way to classify intermediate- and high-risk patients with African ancestry. PATIENTS AND METHODS: This was a retrospective study in an Afro-Caribbean population. A total of 1236 patients were included between 2000 and 2015. Patients were stratified according to (GG). Survival analysis was performed using the Kaplan-Meier method, univariate and multivariate analyses using the Cox model. RESULTS: There was no significant difference at 5 and 10-year BCR-free survival between the intermediate- and high-risk groups, based on the D'Amico classification. There was a highly significant difference in BCR-free survival at 5 (p < 0.0001) and 10 years (p < 0.0001) for patients of GG 1 and 2 vs 3, 4, and 5, respectively. There was no significant difference in 5-year BCR-free survival of patients of GG grades 1 and 2, whether lymph-node dissection was performed or not. There was a significant difference between GG 2 and 3 patients in 5 (p = 0.008) and 10-year BCR-free survival (p = 0.01). High PSA (p < 0.0001), pathological GG ≥ 3 (p < 0.0001), pathological stage pT3 (p < 0.0001) and positive margins (p < 0.0001) were factors for BCR in multivariate analysis. CONCLUSION: The GG 2015 classification appears to be a better prognostic factor than D'Amico classification for intermediate- and high-risk Afro-Caribbean patients.

6.
Prostate ; 80(4): 329-335, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31868959

RESUMO

BACKGROUND: Several studies in the Caucasian population have shown that patients with Gleason 6 prostate cancer, based on surgical specimens, have low or no risk of metastasis. However, there is no data for men of African ancestry. The objective of this study was to estimate the overall, specific, and metastasis-free survival (MFS) of patients with a Gleason 6 score, based on the surgical specimen. PATIENTS AND METHODS: This was a monocentric retrospective study that included 723 consecutive patients treated by radical prostatectomy between 1 January 1 2000 and 31 March 2018, with a Gleason score of 6 based on the surgical specimen. Specific survival (SS) was defined as the time elapsed between surgery and death attributed to prostate cancer. Overall survival was defined as the time elapsed between surgery and death from all causes. The causes of death were verified in the medical records. Survival analyses without biochemical recurrence (BCR) and without salvage treatment were performed according to the Kaplan-Meier method. The Cox model was used for univariate and multivariate analyses. RESULTS: In total, 691 patients were included because 32 were excluded for missing data. Overall 5- and 10-year survival was 94.2% and 87.1%, respectively. SS and MFS were 100%, with a median follow-up of 8.5 years. The BCR rate was 16.5%, with a median time to BCR of 5.1 years. The frequency of salvage treatment was 13.0%, with a median time to surgery of 7.3 years. In univariate analysis, PSA, pathological stage, seminal vesicle invasion, positive margins, and lymph node dissection were significantly associated with an increased risk of BCR and salvage treatment, but only PSA and positive margins were significantly associated by multivariate analysis. DISCUSSION/CONCLUSION: No metastasis or disease-specific deaths were observed for men with Gleason score ≤6 prostate cancer at radical prostatectomy, in particular, men of African ancestry.


Assuntos
Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/mortalidade , Idoso , Região do Caribe/etnologia , Estudos de Coortes , Guadalupe/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida
7.
Int J Cancer ; 146(3): 657-663, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30892691

RESUMO

Previous studies have suggested that exposure to environmental chemicals with hormonal properties, also called endocrine disrupting chemicals, may be involved in the occurrence of prostate cancer (PCa). Such exposure may also influence the treatment outcome as it is still present at the time of diagnosis, the beginning of therapy, and beyond. We followed 326 men in Guadeloupe (French West Indies) who underwent radical prostatectomy as primary treatment of localized PCa. We analyzed the relationship between exposure to the estrogenic chlordecone, the antiandrogenic dichlorodiphenyldichloroethylene (DDE, the main metabolite of the insecticide DDT), and the nondioxin-like polychlorinated biphenyl congener 153 (PCB-153) with mixed estrogenic/antiestrogenic properties and the risk of biochemical recurrence (BCR) after surgery. After a median follow-up of 6.1 years after surgery, we found a significant increase in the risk of BCR, with increasing plasma chlordecone concentration (adjusted hazard ratio = 2.51; 95% confidence interval: 1.39-4.56 for the highest vs. lowest quartile of exposure; p trend = 0.002). We found no associations for DDE or PCB-135. These results shown that exposure to environmental estrogens may negatively influence the outcome of PCa treatment.


Assuntos
Disruptores Endócrinos/efeitos adversos , Poluentes Ambientais/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Prostatectomia , Neoplasias da Próstata/patologia , Idoso , Clordecona/efeitos adversos , Clordecona/sangue , Diclorodifenil Dicloroetileno/efeitos adversos , Diclorodifenil Dicloroetileno/sangue , Intervalo Livre de Doença , Poluentes Ambientais/sangue , Seguimentos , Guadalupe , Humanos , Inseticidas/efeitos adversos , Inseticidas/sangue , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/etiologia , Bifenilos Policlorados/efeitos adversos , Bifenilos Policlorados/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Fatores de Risco
8.
Eur Urol ; 75(1): 11-15, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30245085

RESUMO

Causes of high mortality of prostate cancer in men of African ancestry living in the French West Indies are still debated, between suspicions of environmental factors and genetic susceptibility. We report an integrated genomic study of 25 tumour tissues from radical prostatectomy of aggressive (defined by International Society of Urological Pathology ≥3) prostate cancer patients (10 African Caribbean and 15 French Caucasian) using single nucleotide polymorphism arrays, whole-genome sequencing, and RNA sequencing. The results show that African Caribbean tumours are characterised by a more frequent deletion at 1q41-43 encompassing the DNA repair gene PARP1, and a higher proportion of intrachromosomal rearrangements including duplications associated with CDK12 truncating mutations. Transcriptome analyses show an overexpression of genes related to androgen receptor activity in African Caribbean tumours, and of PVT1, a long non-coding RNA located at 8q24 that confirms the strong involvement of this region in prostate tumours from men of African ancestry. Patient summary: Mortality of prostate cancer is higher in African Caribbean men than in French Caucasian men. Specificities of the former could be explained by genomic events linked with key genes such as DNA damage pathway genes PARP1, CDK12, and the oncogenic long non-coding RNA gene PVT1 at the 8q24 prostate cancer susceptibility locus.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Europeu/genética , Neoplasias da Próstata/genética , Região do Caribe/etnologia , Humanos , Masculino , Mutação , Polimorfismo de Nucleotídeo Único , Prostatectomia , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Sequenciamento Completo do Genoma
9.
J Endourol Case Rep ; 4(1): 111-113, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065958

RESUMO

Background: Pheochromocytomas typically are diagnosed in the adrenal gland and from the sympathetic nervous system. Bladder pheochromocytoma is a rare location for this tumor. Case Presentation: We describe a 67-year-old Afro Caribbean woman referred to our hospital for an asymptomatic bladder tumor. Preliminary transurethral resection revealed bladder pheochromocytoma. After a comprehensive endocrine evaluation, we performed a robot-assisted laparoscopic partial cystectomy with ureteral reimplantation. Conclusion: We present a rare case of bladder pheochromocytoma treated effectively with minimally invasive techniques. When confronted with a solid bladder mass, apart from the more common urothelial malignancies, a differential diagnosis of bladder pheochromocytoma should also be considered.

10.
Eur J Cancer ; 91: 107-115, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29413967

RESUMO

BACKGROUND: Genetic and nutritional factors have been linked to the risk of aggressive prostate cancer (PCa). The fatty acid (FA) composition of peri-prostatic adipose tissue (PPAT), which reflects the past FA intake, is potentially involved in PCa progression. We analysed the FA composition of PPAT, in correlation with the ethno-geographical origin of the patients and markers of tumour aggressiveness. METHODS: From a cohort of 1000 men treated for PCa by radical prostatectomy, FA composition of PPAT was analysed in 156 patients (106 Caucasians and 50 African-Caribbeans), 78 with an indolent tumour (ISUP group 1 + pT2 + PSA <10 ng/mL) and 78 with an aggressive tumour (ISUP group 4-5 + pT3). The effect of FA extracted from PPAT on in-vitro migration of PCa cells DU145 was studied in 72 patients, 36 Caucasians, and 36 African-Caribbeans. RESULTS: FA composition differed according to the ethno-geographical origin. Linoleic acid, an essential n-6 FA, was 2-fold higher in African-Caribbeans compared with Caucasian patients, regardless of disease aggressiveness. In African-Caribbeans, the FA profile associated with PCa aggressiveness was characterised by low level of linoleic acid along with high levels of saturates. In Caucasians, a weak and negative association was observed between eicosapentaenoic acid level (an n-3 FA) and disease aggressiveness. In-vitro migration of PCa cells using PPAT from African-Caribbean patients was associated with lower content of linoleic acid. CONCLUSION: These results highlight an important ethno-geographical variation of PPAT, in both their FA content and association with tumour aggressiveness.


Assuntos
Tecido Adiposo/metabolismo , Grupo com Ancestrais do Continente Africano , Movimento Celular , Grupo com Ancestrais do Continente Europeu , Ácidos Graxos/metabolismo , Neoplasias da Próstata/química , Tecido Adiposo/patologia , Idoso , Linhagem Celular Tumoral , Bases de Dados Factuais , Ácido Eicosapentaenoico/metabolismo , França/epidemiologia , Humanos , Ácido Linoleico/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Comunicação Parácrina , Prostatectomia , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Transdução de Sinais , Índias Ocidentais/epidemiologia
11.
J Urol ; 197(5): 1229-1236, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27993665

RESUMO

PURPOSE: Active surveillance is a treatment option for favorable risk prostate cancer. However, data are missing on populations of African descent. We evaluated the safety and benefit of active surveillance in an African Caribbean cohort with favorable risk prostate cancer. MATERIALS AND METHODS: Between 2005 and 2016, a single center, prospective cohort study was performed in Guadeloupe, French West Indies, including patients on active surveillance who had low risk prostate cancer (prostate specific antigen 10 ng/ml or less and Gleason score 6 or less) or favorable intermediate risk prostate cancer (prostate specific antigen 10 to 20 ng/ml, Gleason score 3 + 4 or less and life expectancy less than 10 years). Treatment was recommended in case of grade progression, increased tumor volume, prostate cancer doubling time less than 36 months or patient wish. Overall survival, disease specific survival and duration of active surveillance were calculated with the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards model to identify predictors of active surveillance termination. RESULTS: A total of 234 patients with a median age of 64 years were enrolled in study. Median followup was 4 years (IQR 2.3-5.5). Overall survival at 30 months, 5 years and 10 years was 99.5%, 98.5% and 90.7%, respectively. Disease specific survival at 30 months, and 5 and 10 years was 100%. At 30 months, 5 years and 10 years 72.7%, 52.6% and 40.4% of patients, respectively, remained untreated and on active surveillance. Age (HR 0.96 per additional year, 95% CI 0.93-0.99) and prostate specific antigen density (HR 1.52 per additional 0.1 ng/ml, 95% CI 1.20-1.89) were found to be independent predictors of active surveillance termination. CONCLUSIONS: Active surveillance is safe and beneficial for highly selected African Caribbean patients. It seems to be feasible for patients at low risk and intermediate favorable risk. Prostate specific antigen density could help better select these patients.


Assuntos
Neoplasias da Próstata/terapia , Conduta Expectante/métodos , Grupo com Ancestrais do Continente Africano , Idoso , Região do Caribe , Estudos de Coortes , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/mortalidade , Medição de Risco/métodos
12.
PLoS One ; 11(5): e0154866, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27145183

RESUMO

OBJECTIVES: To investigate the association between priapism in men with sickle cell anemia (SCA) and hemorheological and hemolytical parameters. MATERIALS AND METHODS: Fifty-eight men with SCA (median age: 38 years) were included; 28 who had experienced priapism at least once during their life (priapism group) and 30 who never experienced this complication (control group). Twenty-two patients were treated with hydroxycarbamide, 11 in each group. All patients were at steady state at the time of inclusion. Hematological and biochemical parameters were obtained through routine procedures. The Laser-assisted Optical Rotational Cell Analyzer was used to measure red blood cell (RBC) deformability at 30 Pa (ektacytometry) and RBC aggregation properties (laser backscatter versus time). Blood viscosity was measured at a shear rate of 225 s-1 using a cone/plate viscometer. A principal component analysis was performed on 4 hemolytic markers (i.e., lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), total bilirubin (BIL) levels and reticulocyte (RET) percentage) to calculate a hemolytic index. RESULTS: Compared to the control group, patients with priapism exhibited higher ASAT (p = 0.01), LDH (p = 0.03), RET (p = 0.03) levels and hemolytic indices (p = 0.02). Higher RBC aggregates strength (p = 0.01) and lower RBC deformability (p = 0.005) were observed in patients with priapism compared to controls. After removing the hydroxycarbamide-treated patients, RBC deformability (p = 0.01) and RBC aggregate strength (p = 0.03) were still different between the two groups, and patients with priapism exhibited significantly higher hemolytic indices (p = 0.01) than controls. CONCLUSION: Our results confirm that priapism in SCA is associated with higher hemolytic rates and show for the first time that this complication is also associated with higher RBC aggregate strength and lower RBC deformability.


Assuntos
Anemia Falciforme/sangue , Agregação Eritrocítica/fisiologia , Deformação Eritrocítica/fisiologia , Eritrócitos/patologia , Hemólise/fisiologia , Priapismo/sangue , Adulto , Anemia Falciforme/patologia , Biomarcadores/sangue , Viscosidade Sanguínea/fisiologia , Hemorreologia/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Priapismo/patologia , Estudos Prospectivos , Reticulócitos/patologia
13.
PLoS One ; 11(4): e0153609, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27074016

RESUMO

BACKGROUND: Estrogens are thought to play a critical role in prostate carcinogenesis. It has been suggested that polymorphisms of genes encoding enzymes involved in estrogen metabolism are risk factors for prostate cancer. However, few studies have been performed on populations of African ancestry, which are known to have a high risk of prostate cancer. OBJECTIVE: We investigated whether functional polymorphisms of CYP17, CYP19, CYP1B1, COMT and UGT1A1 affected the risk of prostate cancer in two different populations of African ancestry. METHODS: In Guadeloupe (French West Indies), we compared 498 prostate cancer patients and 565 control subjects. In Kinshasa (Democratic Republic of Congo), 162 prostate cancer patients were compared with 144 controls. Gene polymorphisms were determined by the SNaPshot technique or short tandem repeat PCR analysis. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The AA genotype and the A allele of rs4680 (COMT) appeared to be inversely associated with the risk of prostate cancer in adjusted models for both Afro-Caribbean and native African men. For the A allele, a significant inverse association was observed among cases with low-grade Gleason scores and localized clinical stage, in both populations. CONCLUSIONS: These preliminary results support the hypothesis that polymorphisms of genes encoding enzymes involved in estrogen metabolism may modulate the risk of prostate cancer in populations of African ancestry.


Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Adulto , Grupo com Ancestrais do Continente Africano/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Aromatase/genética , Estudos de Casos e Controles , Catecol O-Metiltransferase/genética , Citocromo P-450 CYP1B1/genética , República Democrática do Congo , Estudos de Associação Genética , Genótipo , Glucuronosiltransferase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Esteroide 17-alfa-Hidroxilase/genética , Índias Ocidentais
14.
Environ Sci Pollut Res Int ; 23(1): 3-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25940496

RESUMO

Chlordecone (Kepone) is an organochlorine insecticide that has been used as insecticide and fungicide. In the French West Indies, Guadeloupe and Martinique, it was intensively applied to banana fields from 1973 to 1993 to control root borers. This pesticide undergoes no significant biotic or abiotic degradation in the environment and is still present in soils where it was applied. It was only in 1999 that health and environmental authorities became aware of the extent of the chlordecone pollution of environmental media, including soils, waterways, and the food chain. Earlier observations and toxicological studies have demonstrated that chlordecone is a reproductive and developmental toxicant, neurotoxic and carcinogenic in rodents, and is an endocrine-disrupting chemical because of its estrogenic properties both in vitro and in vivo. Several surveys have confirmed that the French West Indian population continues to be exposed to this chemical though consumption of contaminated foodstuffs. Here, we report the findings of various epidemiological studies conducted in the French West Indies to assess the impact of environmental exposure to chlordecone on the health of the population.


Assuntos
Clordecona/toxicidade , Exposição Ambiental , Inseticidas/toxicidade , Adulto , Animais , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Clordecona/análise , Disruptores Endócrinos/toxicidade , Feminino , Fertilidade/efeitos dos fármacos , Guadalupe , Humanos , Inseticidas/análise , Masculino , Martinica , Musa , Gravidez , Complicações na Gravidez/induzido quimicamente , Solo/química , Poluentes do Solo/análise , Índias Ocidentais
15.
Urol Oncol ; 33(5): 202.e9-17, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25746940

RESUMO

BACKGROUND: The paradigm change observed over the last few years in several solid tumors emphasizes the value of locoregional treatment in the presence of metastatic disease, currently ignored in de novo prostate cancer (CaP). We investigated the effect of the primary tumor that is left untreated on prostate cancer-specific morbidity and mortality, time to castration resistance, and overall survival (OS). METHODS: We performed a bicentric cohort study. The overall population included de novo metastatic CaP managed at the Genito-Urinary Oncology Unit of the Gustave Roussy Institute and the Urology Clinic of the University Hospital of Pointe-à-Pitre, France. Descriptive statistical and outcome analyses were performed in the overall cohort and also separately in the N+M0 and M+subgroups. RESULTS: The overall cohort included 263 patients. Approximately two-thirds of patients (64%) presented with locoregional symptoms at diagnosis, and 78% throughout the disease. Of the symptomatic patients, 59% required a locoregional procedure. Median OS of patients with locoregional symptoms at diagnosis was shorter than in those who were asymptomatic (47 vs. 86 mo, P = 0.0007); this difference was maintained in the N+M0 and M+subgroups. Median OS and time to castration resistance showed a nonsignificant trend in favor of patients undergoing a locoregional treatment at diagnosis. CONCLUSION: The presence of symptoms due to locoregional disease in de novo metastatic CaP entails significant morbidity and even mortality and requires active management. Randomized prospective trials are needed to evaluate the role of initial definite locoregional treatment in these patients.


Assuntos
Neoplasias da Próstata/patologia , Idoso , Estudos de Coortes , Gerenciamento Clínico , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias da Próstata/mortalidade , Resultado do Tratamento
16.
Asian J Androl ; 17(1): 117-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25130587

RESUMO

Multiple regions of the genome have been associated with the risk of prostate cancer in Caucasians, particularly including several polymorphisms located at 8q24. Region 2 of 8q24 has been repeatedly found to be associated with the risk of prostate cancer among men of African descent, although one study performed in the Caribbean island of Jamaica did not report this finding. In this study, the single nucleotide polymorphism rs16901979, located in region 2 of 8q24, was genotyped in 498 cases of histologically confirmed prostate cancer and 541 controls from the French Caribbean islands of Guadeloupe, where the population is largely of African descent. The AA genotype and the A allele at rs16901979 were associated with elevated risks of prostate cancer (odds ratios [ORs] = 1.84, 95% confidence interval [95% CI] = 1.26-2.69, P = 0.002 and OR = 1.36, 95% CI = 1.13-1.64, P = 0.001, respectively). Following stratification of the patients by disease aggressiveness, as defined by the Gleason score, the pooled genotypes AC + AA were associated with a higher risk of a Gleason score ≥7 at diagnosis (OR = 1.79, 95% CI = 1.17-2.73, P = 0.007). In summary, the A allele at rs16901979 was associated with the risk of prostate cancer in the Caribbean population of Guadeloupe, confirming its involvement in populations of African descent. Moreover, our study provides the first evidence of an association between this variant and the risk of aggressive prostate cancer.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Cromossomos Humanos Par 8/genética , Predisposição Genética para Doença/genética , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Grupo com Ancestrais do Continente Africano/etnologia , Idoso , Alelos , Estudos de Casos e Controles , Progressão da Doença , Genótipo , Guadalupe , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/etnologia , Fatores de Risco , Índice de Gravidade de Doença
17.
Environ Health Perspect ; 123(4): 317-23, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25493337

RESUMO

BACKGROUND: Long-term exposure to persistent pollutants with hormonal properties (endocrine-disrupting chemicals; EDCs) may contribute to the risk of prostate cancer (PCa). However, epidemiological evidence remains limited. OBJECTIVES: We investigated the relationship between PCa and plasma concentrations of universally widespread pollutants, in particular p,p'-dichlorodiphenyl dichloroethene (DDE) and the non-dioxin-like polychlorinated biphenyl congener 153 (PCB-153). METHODS: We evaluated 576 men with newly diagnosed PCa (before treatment) and 655 controls in Guadeloupe (French West Indies). Exposure was analyzed according to case-control status. Associations were assessed by unconditional logistic regression analysis, controlling for confounding factors. Missing data were handled by multiple imputation. RESULTS: We estimated a significant positive association between DDE and PCa [adjusted odds ratio (OR) = 1.53; 95% CI: 1.02, 2.30 for the highest vs. lowest quintile of exposure; p trend = 0.01]. PCB-153 was inversely associated with PCa (OR = 0.30; 95% CI: 0.19, 0.47 for the highest vs. lowest quintile of exposure values; p trend < 0.001). Also, PCB-153 was more strongly associated with low-grade than with high-grade PCa. CONCLUSIONS: Associations of PCa with DDE and PCB-153 were in opposite directions. This may reflect differences in the mechanisms of action of these EDCs; and although our findings need to be replicated in other populations, they are consistent with complex effects of EDCs on human health.


Assuntos
Diclorodifenil Dicloroetileno/sangue , Bifenilos Policlorados/sangue , Neoplasias da Próstata/induzido quimicamente , Idoso , Estudos de Casos e Controles , Diclorodifenil Dicloroetileno/toxicidade , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/efeitos adversos , Guadalupe/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Bifenilos Policlorados/toxicidade , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Fatores de Risco
18.
Prostate ; 74(15): 1481-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25175352

RESUMO

BACKGROUND: TMPRSS2/ERG fusion resulting in ERG overexpression occurs in 30 to 50% of prostate cancer (PCa) in Caucasian patients, but its prognostic relevance remains controversial. In the present study, we investigated ERG expression in all stages of PCa progression, and evaluated the prognostic impact of ERG status in clinically localized PCa (CLC) and in castration resistant disease (CRPC). METHODS: ERG and AR expressions were evaluated by immunohistochemistry on tissue microarrays containing samples of high grade PIN (n = 57), CLC surgically treated (n = 299, including 185 Caucasians and 114 African-Caribbeans), metastases (n = 17), and CRPC (n = 41). RESULTS: In Caucasians, ERG expression significantly increased from high grade PIN (17.5%) to pT2 (27%) and pT3 CLC (43%), then to metastases (53%). In CLC, stainings for ERG and AR were correlated, and ERG expression was less frequent in African-Caribbeans compared to Caucasians (11.5% vs. 33%). In Caucasians CLC, ERG was associated with longer recurrence free survival, after adjusting for classical prognostic markers. In CRPC, ERG was expressed in 29% of cases, and was associated with a longer overall survival. CONCLUSIONS: Our results confirm that ERG expression is less frequent in PCa from patients of African descent. Although ERG expression increases during PCa natural history, positive ERG status is associated with better outcome in both CLC and CRPC. This paradox could be explained in part by the fact that ERG expression is AR dependant, then ERG positive cancers are likely to progress in a rich androgen environment, with a better response to androgen suppression.


Assuntos
Biomarcadores Tumorais/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Receptores Androgênicos/metabolismo , Transativadores/metabolismo , Idoso , Grupos Étnicos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata/metabolismo , Neoplasias da Próstata/patologia , Análise Serial de Tecidos , Regulador Transcricional ERG
19.
PLoS One ; 9(9): e107275, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25198353

RESUMO

BACKGROUND: Deletions of the glutathione S-transferase genes M1 and T1 (GSTM1 and GSTT1) have been studied as potential risk factors for prostate cancer. Conflicting results have been obtained. Moreover, most such studies could not discriminate heterozygous from homozygous carriers of the non-deleted alleles. OBJECTIVE: We investigated whether copy number variation (CNV) of the GSTM1 and/or GSTT1 genes contribute to the risk of prostate cancer in the Caribbean population of African descent of Guadeloupe. METHODS: In a population-based case-control study, we compared 629 prostate cancer patients and 622 control subjects. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Exact copy numbers of GSTM1 and GSTT1 were determined by real-time PCR. RESULTS: A higher copy number of GSTM1 was marginally associated with prostate cancer risk. Men with 2 and 3 or more GSTT1 genes were at higher risk of prostate cancer (OR: 1.55, 95% CI: 1.11-2.16 and OR: 4.89, 95% CI: 1.71-13.99, respectively; P(trend)<0.001). Men with 3, 4 and 5 or more copies of both GSTM1 and GSTT1 genes were at higher risk of prostate cancer (OR: 2.18, 95% CI: 1.21-3.91, OR: 3.24, 95% CI: 1.63-6.46, and OR: 5.77, 95% CI: 1.40-23.84, respectively; P(trend)<0.001). CONCLUSIONS: Copy number of GSTT1 and combined GSTM1/GSTT1 appear to be associated with prostate cancer risk in our population study with gene dose relationship. Our results support the hypothesis that variations in copy number of GSTT1 modulate the risk of prostate cancer.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Variações do Número de Cópias de DNA , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Região do Caribe/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/etnologia
20.
Korean J Urol ; 55(2): 145-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24578813

RESUMO

Translocation renal cell carcinoma (RCC) is a family of rare tumors recently identified in the pediatric and young adult population. We report the first case of a young woman from French West Indies with sickle cell anemia who developed a translocation RCC t(6;11)(p21;q12). Usually people with the sickle cell condition are known to develop renal medullary carcinoma (RMC). To our knowledge, this is the first case described in the literature of a translocation RCC associated with sickle cell disease. Here we discuss the relation between translocation RCC, RMC, and sickle cell disease.

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