Éditeur(s) : Université des Antilles AREBio Groupe de recherche BIOSPHERES : BIOlogie, Sciences Physiques & Humaines pour les énergies Renouvelables, l
Extrait de : 1er colloque international BIOSPHERES, du 18 au 20 juin 2019. Université des Antilles
Description : This study provides detailed data regarding the quality of diagnosis and management of patients with prostate cancer in Martinique. Providing data on prostate cancer is essential for the development of high-priority public health measures for the Caribbean.

Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V19082
V19082

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
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 KaplanMeier 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.
ISSN: 0022-5347

hal-01519251
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01519251
DOI : 10.1016/j.juro.2016.12.047
PUBMED : 27993665

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Prostate cancer disparities have been reported in men of African descent who show the highest incidence, mortality, compared with other ethnic groups. Few studies have explored the genetic and environmental factors for prostate cancer in men of African ancestry. The glutathione-S-transferases family conjugates carcinogens before their excretion and is expressed in prostate tissue. This study addressed the role of GSTM1 and GSTT1 deletions on prostate cancer risk in populations of African descent. This multi-institutional case-control study gathered data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database, the African-Caribbean Cancer Consortium (AC3) and Men of African Descent and Carcinoma of the Prostate Consortium (MADCaP). The analysis included 10 studies (1715 cases and 2363 controls), five in African-Americans, three in African-Caribbean and two in African men. Both the GSTM1 and the GSTT1 deletions showed significant inverse associations with prostate cancer [odds ratio (OR): 0.90, 95% confidence interval (CI) 0.83-0.97 and OR 0.88, 95% CI: 0.82-0.96, respectively]. The association was restricted to Caribbean and African populations. A significant positive association was observed between GSTM1 deletion and prostate cancer in smokers in African-American studies (OR: 1.28, 95% CI: 1.01-1.56), whereas a reduced risk was observed in never-smokers (OR: 0.66, 95% CI: 0.46-0.95). The risk of prostate cancer increased across quartiles of pack-years among subjects carrying the deletion of GSTM1 but not among subjects carrying a functional GSTM1. Gene-environment interaction between smoking and GSTM1 may be involved in the etiology of prostate cancer in populations of African descent.
ISSN: 0143-3334

hal-00682901
https://hal.archives-ouvertes.fr/hal-00682901
DOI : 10.1093/carcin/bgr119
PUBMED : 21705483

Éditeur(s) : Université des Antilles AREBio Groupe de recherche BIOSPHERES : BIOlogie, Sciences Physiques & Humaines pour les énergies Renouvelables, l
Extrait de : 1er colloque international BIOSPHERES, du 18 au 20 juin 2019. Université des Antilles
Description : Chlordecone is a persistent organochlorine pesticide widely used between 1972 and 1993 in the French West Indies to control the root borer in banana fields. Chlordecone use resulted in long-term pollution of soils, contamination of waters, of aquatic organisms, and of fields. Chlordecone is known to be neurotoxic, to increase prostate cancer, and to have negative effects on cognitive and motor development during infancy. In Guadeloupe, most of the freshwater species living in contaminated rivers exceed the French legal limit of 20 ?g·kg?1 wet weight. In the present study (ANR MACHLOMA), we chose a transcriptomic approach to study the cellular effects of chlordecone in the giant freshwater prawn Macrobrachium rosenbergii, an important economical species in Guadeloupe.

Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V19065
V19065

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
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
ISSN: 1932-6203

hal-01305477
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01305477
DOI : 10.1371/journal.pone.0153609
PUBMED : 27074016

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: Cancer/Testis (CT) genes are expressed in male gonads, repressed in most healthy somatic tissues and de-repressed in various somatic malignancies including prostate cancers (PCa). Because of their specific expression signature and their associations with tumor aggressiveness and poor outcomes, CT genes are considered to be useful biomarkers and they are also targets for the development of new anti-cancer immunotherapies. The aim of this study was to identify novel CT genes associated with hormone-sensitive prostate cancer (HSPC), and castration-resistant prostate cancer (CRPC). METHODS: To identify novel CT genes we screened genes for which transcripts were detected by RNA profiling specifically in normal testis and in either HSPC or CRPC as compared to normal prostate and 44 other healthy tissues using GeneChips. The expression and clinicopathological significance of a promising candidate-NR6A1-was examined in HSPC, CRPC, and metastatic site samples using tissue microarrays. RESULTS: We report the identification of 98 genes detected in CRPC, HSPC and testicular samples but not in the normal controls. Among them, cellular levels of NR6A1 were found to be higher in HSPC compared to normal prostate and further increased in metastatic lesions and CRPC. Furthermore, increased NR6A1 immunoreactivity was significantly associated with a high Gleason score, advanced pT stage and cancer cell proliferation. CONCLUSIONS: Our results show that cellular levels of NR6A1 are correlated with disease progression in PCa. We suggest that this essential orphan nuclear receptor is a potential therapeutic target as well as a biomarker of PCa aggressiveness. Prostate © 2013 Wiley Periodicals, Inc.
ISSN: 0270-4137

inserm-00821963
http://www.hal.inserm.fr/inserm-00821963
DOI : 10.1002/pros.22659
PUBMED : 23532770

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
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.
ISSN: 1932-6203

hal-01668333
https://hal.univ-antilles.fr/hal-01668333
DOI : 10.1371/journal.pone.0153609
PUBMED : 27074016

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Introduction. - Temocillin is an alternative to treat urinary tract infections with bacteria producing extended spectrum beta-lactamase (ESBL). The objective is to evaluate the use of temocillin in urinary tract infections. Materials and methods. - A systematic review of literature was carried out according to PRISMA criteria. All national and international recommendations have been reviewed regarding the indication of the use of temocillin in urology. Data collection on the use of temocillin in urinary tract infection has been performed from the Cochrane, LILACS and the Medline database. The following keywords were used: temocillin, extended spectrum. beta-lactamase, urinary tract infections, urine, prostate, epididymis, testis, diffusion, pharmacokinetics, pharmacodynamics. The selection was based on the methodology, language of publication (English/French), relevance to the topic and date of publication of the articles collected. The endpoint was to provide exhaustive scientific information allowing urologists to use this antibiotic in febrile urinary infections. Results. - Bacteria producing ESBL has a relatively high susceptible to temocillin, ranging from 61 % to 90 %. These rates would allow its use in probabilistic. The dosage recommended is currently, in the normo-renal patient, 4 g per day by intermittent infusion or continuously after a loading dose of 2g. Some studies argue, particularly in case of difficult clinical situations or obese patients, for administration of high doses (6 g/24 h) rather continuous infusion. There is no evident relationship between high doses and side effects. With an excellent urinary and prostatic diffusion, temocilllin might be recommend for the treatment of ESBL prostatitis. Conclusion. - Temocillin is known to have good urinary and prostatic diffusion. According to our results, this antibiotics is now a reliable alternative for the treatment of documented ESBL urinary tract infections. (C) 2017 Elsevier Masson SAS. All rights reserved.
ISSN: 1166-7087

hal-01659245
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01659245
DOI : 10.1016/j.purol.2017.07.242
PUBMED : 28869169

Éditeur(s) : Université des Antilles AREBio Groupe de recherche BIOSPHERES : BIOlogie, Sciences Physiques & Humaines pour les énergies Renouvelables, l
Extrait de : 1er colloque international BIOSPHERES, du 18 au 20 juin 2019. Université des Antilles

Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V19083
V19083

Éditeur(s) : HAL CCSD Medknow Publications
Résumé : International audience
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.
ISSN: 1008-682X

Droits : http://creativecommons.org/licenses/by-nc-sa/
hal-01118552
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118552
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118552/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118552/file/AsianJAndrol171117-1705456_044414.pdf
DOI : 10.4103/1008-682X.135127

Éditeur(s) : HAL CCSD
Résumé : International audience
To study the associations between occupation, industry and prostate cancer risk in Guadeloupe, a high incidence area. Incident cases of prostate cancer (707 cases) and 722 population controls were included. Information on lifetime occupational history and other potential risk factors was collected by interview. Logistic regression was used to estimate adjusted odds-ratios (OR) and their 95% confidence intervals (CI). A significantly decreased risk was observed in farmers (OR=0.5; CI 0.4-0.7), whereas marginally elevated ORs were found for farm workers, especially in sugarcane and banana farming. Banana plantation workers had been exposed to chlordecone, an estrogenic insecticide previously found to be associated with prostate cancer risk in this population. Significantly increased risks of prostate cancer were found in stock clerks (OR=2.7; CI 1.0-7.2), fishermen (OR=2.0; CI 1.0-4.0), mail distribution clerks (OR=7.7; CI 1.7-34.4) and electricians employed for more than 20 years (OR=4.0; CI 1.0-15.8), as well as in public administration (OR=1.8; CI 1.2-2.9), retail trade (OR=2.6; CI 1.1-6.0) and manufacture of food products (OR=2.0; CI 1.1-3.9), particularly sugar (OR=13.2; IC 1.6-108). Non-significantly elevated ORs were also seen for construction workers and transport equipment operators. Although the overall findings suggest that occupational factors have only a limited role in prostate cancer aetiology, elevated risks of prostate cancer were found in several occupations or industries. Exposure to pesticides, solvents, traffic-related air pollution, low physical activity, whole-body vibration may explain some of these increased risks.
Challenges for Occupational Epidemiology in the 21st Century EPICOH 2014
Chicago, United States

hal-01118558
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118558
DOI : 10.1136/oemed-2014-102362.312
PUBMED : 25018167

Éditeur(s) : HAL CCSD National Institute of Environmental Health Sciences (NIEHS) National Institute of Environmental Health Sciences
Résumé : International audience
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. 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 (PCB153). We evaluated before treatment 576 men with newly diagnosed PCa 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. 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 versus lowest quintile of exposure; PTrend = 0.01). PCB153 was inversely associated with PCa (OR 0.30; 95% CI 0.19, 0.47 for the highest versus lowest quintile of exposure values; PTrend < 0.001). Also, PCB153 was more strongly associated to low-grade than high grade PCa. Associations of PCa with DDE and PCB153 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.
ISSN: 0091-6765

hal-01118553
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118553
DOI : 10.1289/ehp.1408407
PUBMED : 25493337

Éditeur(s) : HAL CCSD American Society of Clinical Oncology
Résumé : International audience
PURPOSE: Determining whether environmental estrogens are associated with the risk of prostate cancer may have important implications for our general understanding of this disease. The estrogenic insecticide chlordecone was used extensively in the French West Indies, contaminating the population for more than 30 years. We analyzed the relationship between exposure to chlordecone and the risk of prostate cancer. PATIENTS AND METHODS: We investigated 623 men with prostate cancer and 671 controls. Exposure was analyzed according to case-control status, using either current plasma concentration or a cumulative exposure index based on years of exposure. We genotyped two single-nucleotide polymorphisms (rs3829125 and rs17134592) in the gene encoding chlordecone reductase. RESULTS: We found a significant increase in the risk of prostate cancer with increasing plasma chlordecone concentration (odds ratio [OR], 1.77; 95% CI, 1.21 to 2.58 for the highest tertile of values above the limit of detection [LD]; P trend = .002) and for cumulative exposure index (OR, 1.73; 95% CI, 1.04 to 2.88 for the highest quartile; P trend = .004). Stronger associations were observed among those with a positive family history of prostate cancer and among those who had lived in a Western country. The rs3829125 and rs17134592 allele variants were in complete linkage disequilibrium and were found at low frequency (0.04). Among subjects with plasma chlordecone concentrations above the LD, carriers of the allele variants had a higher risk of prostate cancer (OR, 5.23; 95% CI, 0.82 to 33.32). CONCLUSION: These findings support the hypothesis that exposure to environmental estrogens increases the risk of prostate cancer.
ISSN: 0732-183X

inserm-00518099
http://www.hal.inserm.fr/inserm-00518099
DOI : 10.1200/JCO.2009.27.2153
PUBMED : 20566993

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : Le cancer de la prostate est le cancer le plus fréquent chez l'homme dans la majorité des pays occidentaux. Certains facteurs de risque sont bien identifiés (âge, antécédents familiaux, origine ethnique) mais son étiologie reste largement méconnue. Les substances chimiques d'origine anthropique suscitent de nombreuses interrogations quant à leur rôle dans la survenue de la maladie. Divers travaux ont montré, de manière consistante, la présence d'un excès de risque de cancer de la prostate chez les populations agricoles par rapport à la population générale. Cependant, l'hypothèse qu'un tel excès de risque soit relié à l'utilisation de pesticides n'a pas encore été formellement démontrée.
ISSN: 1166-7087

hal-00671956
https://hal.archives-ouvertes.fr/hal-00671956

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
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; Ptrend extless0.001). 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; Ptrend extless0.001). 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.
ISSN: 1932-6203

hal-01063905
https://hal.archives-ouvertes.fr/hal-01063905
DOI : 10.1371/journal.pone.0107275
PUBMED : 25198353

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB) and bisphenol A diglycidyl ether (BADGE) at 10(-9)-10(-5) M for 24 or 48 h. Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase three immunohistochemistry), and the levels of testosterone, INSL3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). A significant dose-dependent inhibition was found between testosterone levels measured in the culture medium and concentrations of BPA (P = 0.00778 at 24 h and P = 0.0291 at 48 h), BPE (P = 0.039) and BPF (P = 0.00663). The observed BPA and BPA-A-induced inhibition of testosterone production varied according to duration of exposure and BPA/BPA-A concentrations. BPA (10(-9) M; P < 0.05), BPB (10(-9) M; P < 0.05), BPS (10(-9) and 10(-8) M; P < 0.05) and BADGE (10(-5) M; P < 0.05) increased Leydig cell INSL3 production. By contrast, BPE dose dependently inhibited INSL3 (P = 0.0372). Conversely, Sertoli cell function (inhibin B) and germ cell viability were not significantly affected by either bisphenols. N/A. Environmental compounds cannot be deliberately administered to men, justifying the use of an ex vivo approach. A relatively low number of testes samples were available for analysis (n = 3, except for testosterone secretion with n = 5). The active concentrations of BPA and BPA-A used in the study were higher than those found in human biological fluids. Under our experimental conditions, direct exposure to BPA or BPA-A can result in endocrine disturbance in the adult human testis.
ISSN: 0268-1161

hal-01578582
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578582/file/Parallel%20assessment%20of%20the%20effects%20of%20bisphenol%20A_accepted.pdf
DOI : 10.1093/humrep/dex093

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
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). 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). 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. 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.
ISSN: 0270-4137

hal-01118555
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118555
DOI : 10.1002/pros.22863
PUBMED : 25175352

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
STUDY QUESTION: Can protein biomarkers of the male genital tract be identified in human seminal plasma? SUMMARY ANSWER: We identified potential biomarkers for each of the organs participating in the secretions of the human seminal plasma. WHAT IS KNOWN ALREADY: The seminal plasma fulfills critical functions for fertility by providing spermatozoa with a protective milieu, promoting their final maturation and modulating the immune responsiveness of the female reproductive tract. It is also considered to be a promising source of biomarkers of male infertility and/or pathologies of the male genital tract. STUDY DESIGN, SIZE, DURATION: This study combines proteomic analyses of normal seminal plasma together with transcriptomic gene expression profiling of human healthy tissues. MATERIALS, SETTING, METHODS: Non-liquefied seminal plasma proteins from a healthy donor were prefractionated using two sequential Proteominer™ libraries. Eight subproteome fractions were collected, trypsin digested and subjected to three successive mass spectrometry analyses for peptide characterization. The list of identified proteins was compared with and merged with other available data sets of the human seminal plasma proteome. The expression of corresponding genes was then investigated using tissue transcriptome profiles to determine where, along the male reproductive tract, these proteins were produced. Finally, tissue specificity of a selected subset of biomarker candidates was validated on human tissues. MAIN RESULTS AND THE ROLE OF CHANCE: We first performed a proteomic analysis of the human seminal plasma and identified 699 proteins. By comparing our protein list with other previous proteomic data sets, we found that 2545 unique proteins have been described so far in the human seminal plasma. We then profiled their expression at the gene level and identified 83 testis, 42 epididymis, 7 seminal vesicle and 17 prostate candidate protein markers. For a subset of testis-specific candidates, i.e. TKTL1, LDHC and PGK2, we further validated their germ cell expression and demonstrated that such markers could distinguish between semen from fertile and infertile men. LIMITATIONS, REASONS FOR CAUTION: While some of the markers we identified are well-known tissue-specific products, further dedicated studies to validate the biomarker status of new candidates will be required. Additionally, whether or not the abundance of these proteins is indeed decreased in some specific pathological situations remains to be determined. WIDER IMPLICATIONS OF THE FINDINGS: Using an integrative genomics approach, we identified biomarker candidates for each of the organs participating in the seminal plasma production. In this study, we essentially focused on germ cell markers and their potential application for the diagnosis of male infertility. Other types of markers also deserve a focused attention given their potential predictive value for various reproductive disorders, notably for prostate cancers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Proteomics Core Facility at Biogenouest and was funded by Conseil Régional de Bretagne, IBiSA and Agence de la Biomédecine grants. The authors declare that there exists a competing financial interest in this work that is related to a patent application on the use of identified germ cell-specific proteins in an antibody-based assay (Fertichip™) to predict the successful testicular biopsy outcomes in human non-obstructive azoospermia.
ISSN: 0268-1161

inserm-00814146
http://www.hal.inserm.fr/inserm-00814146
DOI : 10.1093/humrep/des360
PUBMED : 23024119

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
OBJECTIVES: To investigate whether the glutathione S-transferase polymorphisms GSTM1 and/or GSTT1 contribute to prostate cancer risk in a Caribbean population of African descent in Guadeloupe. METHODS: We performed a hospital-based case-control study with 134 prostate cancer patients and 134 cancer-free, age-matched control subjects. Epidemiologic data were collected using a standard questionnaire. Logistic regression was used to estimate odds ratios (ORs) and compute confidence intervals (CIs). Genotypes were determined by multiplex polymerase chain reaction. RESULTS: The frequency of the GSTM1-positive genotype was 81% in patients and 73% in control subjects, with an adjusted OR of 1.4 (95% CI 0.7 to 2.5). The frequency of the GSTT1-positive genotype was 78% in patients and 63% in control subjects, with an adjusted OR of 2.6 (95% CI 1.4 to 4.9). CONCLUSIONS: A functional GSTT1 polymorphism may be associated with prostate cancer susceptibility in a Caribbean population of African descent.
ISSN: 0090-4295

hal-00688449
https://hal.archives-ouvertes.fr/hal-00688449
DOI : 10.1016/j.urology.2007.02.039
PUBMED : 17572208

Éditeur(s) : HAL CCSD John Libbey Eurotext
Résumé : International audience
In mainland France, as in most Western countries, prostate cancer is the most frequent cancer in men. However, the incidence of this cancer is highly variable, depending on the region of the world. This variability is largely accounted for by differences in access to care, but also by environmental conditions and the ethnogeographic origins of the populations. The French West Indies--the archipelago of Guadeloupe and the island of Martinique--are unique in terms of their geography, environment and the lifestyle and origins of their populations. We report the incidence and mortality rates for prostate cancer in the French West Indies and also provide the first description of the major clinical and anatomical characteristics of this disease in this region.
ISSN: 0007-4551

hal-00671140
https://hal.archives-ouvertes.fr/hal-00671140
DOI : 10.1684/bdc.2008.0811
PUBMED : 19258223