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.
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.
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).
These findings support the hypothesis that exposure to environmental estrogens increases the risk of prostate cancer.
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.
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.
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.
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.
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.
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.
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).
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.
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.
Purpose We determined the impact of increasing the number of cores from 12 to 20 at initial prostate biopsy in men suspicious of prostate cancer. Materials and Methods From December 2009 to November ...2011, patients in 7 centers scheduled for a first prostate biopsy, with a prostate specific antigen less than 20 ng/ml and no nodule on digital rectal examination, were invited to participate in this superiority trial. Patients were randomized to a 12-core (PB12 group) or a 20-core (PB20 group) protocol. The primary end point was cancer detection rate. Secondary end points were cancer characteristics, rate of complications and patient tolerance assessed by a self-completed booklet before prostate biopsy and at day 5 and day 15. Results A total of 339 patients were randomized. Preoperative variables were similar in both groups. Cancer was detected in 71 patients (42.0%) in PB12 group and in 81 patients (48.8%) in PB20 group, and the difference was not significant (p >0.2). Gleason score and cancer length measured on prostate biopsy cores were not significantly different between groups. Although the cancer detection rate was linked to prostate volume, this was not affected by the number of extracted cores (p >0.4). Complications number and seriousness were comparable in both arms. No significant difference was noted regarding side effects and tolerance as self-assessed by the patient at day 5 and day 15 after prostate biopsy. Conclusions Our findings suggest that there is no significant advantage in using a 20-core biopsy protocol vs 12-core protocol during an initial prostate biopsy.
To investigate the association between priapism in men with sickle cell anemia (SCA) and hemorheological and hemolytical parameters.
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.
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.
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.
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.
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.
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.
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.
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).
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.
Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been ...limited to a small number of hormones and reported conflicting results.
We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone.
We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples.
DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone.
These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease.
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.
Abstract 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.
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