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 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
Objectives: Using in silico simulations from histopathological cancer prostate specimen, the objectives were to identify the total dose corresponding to various fractionations necessary to destroy the tumor cells (50% to 99.9%) and to assess the impact of the Gleason score on those doses. © 2017 IEEE.
14th IEEE International Symposium on Biomedical Imaging, ISBI 2017
Melbourne, Australia

hal-01618934
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01618934
DOI : 10.1109/ISBI.2017.7950643

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 Nature Publishing Group
Résumé : International audience
Androgen signaling, via the androgen receptor (AR), is crucial in mediating prostate cancer (PCa) initiation and progression. Identifying new downstream effectors of the androgens/AR pathway will allow a better understanding of these mechanisms and could reveal novel biomarkers and/or therapeutic agents to improve the rate of patient survival. We compared the microRNA expression profiles in androgen-sensitive LNCaP cells stimulated or not with 1 nM R1881 by performing a high-throughput reverse transcriptase-quantitative PCR and found that miR-135a was upregulated. After androgen stimulation, we showed that AR directly activates the transcription of miR-135a2 gene by binding to an androgen response element in the promoter region. Our findings identify miR-135a as a novel effector in androgens/AR signaling. Using xenograft experiments in chick embryos and adult male mice, we showed that miR-135a overexpression decreases in vivo invasion abilities of prostate PC-3 cells. Through in vitro wound-healing migration and invasion assays, we demonstrated that this effect is mediated through downregulating ROCK1 and ROCK2 expression, two genes that we characterized as miR-135a direct target genes. In human surgical samples from prostatectomy, we observed that miR-135a expression was lower in tumoral compared with paired adjacent normal tissues, mainly in tumors classified with a high Gleason score (⩾8). Moreover, miR-135a expression is lower in invasive tumors, showing extraprostatic extension, as compared with intraprostatic localized tumors. In tumor relative to normal glands, we also showed a more frequently higher ROCK1 protein expression determined using a semi-quantitative immunohistochemistry analysis. Therefore, in tumor cells, the lower miR-135a expression could lead to a higher ROCK1 protein expression, which could explain their invasion abilities. The highlighted relationship between miR-135a expression level and the degree of disease aggressiveness suggests that miR-135a may be considered as a prognostic marker in human PCa.Oncogene advance online publication, 28 July 2014; doi:10.1038/onc.2014.222.
ISSN: 0950-9232

hal-01063902
https://hal.archives-ouvertes.fr/hal-01063902
https://hal.archives-ouvertes.fr/hal-01063902/file/Androgen-regulated%20microRNA-135a.pdf
DOI : 10.1038/onc.2014.222
PUBMED : 25065599

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