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Serum lipids and prostate cancer.
Garrido, MM, Marta, JC, Ribeiro, RM, Pinheiro, LC, Guimarães, JT
Journal of clinical laboratory analysis. 2021;(4):e23705
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BACKGROUND Conflicting results are found in the literature relating serum lipids levels and prostate cancer. Some results imply a relationship between them; others contradict this association. The purpose of this study was to investigate a possible association between serum lipids levels and prostate cancer, at time of diagnosis. METHODS We measured serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides in 237 patients submitted to a prostate biopsy, with PSA between 2 and 10 ng/ml. Patients without cancer at biopsy were used as controls, and the others were considered as cases. No information about lipid-lowering therapy, including statins, was available neither in cases nor in controls. Cases were divided into risk groups, according to the disease severity, based on staging. Lipids levels were compared between groups, using parametric and nonparametric tests. Logistic regression analysis and odds ratios were calculated. RESULTS LDL and total cholesterol levels were lower in patients with cancer, with the difference being statistically significant for LDL cholesterol (p = 0.010) and borderline for total cholesterol (p = 0.050). No significant differences were found between the several risk groups. Odds ratios for low LDL cholesterol (<130 mg/dl) and low total cholesterol (<200 mg/dl), with prostate cancer as the outcome, were 1.983 and 1.703, respectively. There were no significant differences between cases and controls for the other lipids. CONCLUSION Lower LDL cholesterol (<130 mg/dl) and lower total cholesterol (<200 mg/dl) serum levels seem to associate with prostate cancer, at time of diagnosis.
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Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study.
Adams, CD, Richmond, R, Ferreira, DLS, Spiller, W, Tan, V, Zheng, J, Würtz, P, Donovan, J, Hamdy, F, Neal, D, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2019;(1):208-216
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BACKGROUND Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR). METHODS The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. RESULTS Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. CONCLUSIONS We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. IMPACT The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
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The role of plasma microseminoprotein-beta in prostate cancer: an observational nested case-control and Mendelian randomization study in the European prospective investigation into cancer and nutrition.
Smith Byrne, K, Appleby, PN, Key, TJ, Holmes, MV, Fensom, GK, Agudo, A, Ardanaz, E, Boeing, H, Bueno-de-Mesquita, HB, Chirlaque, MD, et al
Annals of oncology : official journal of the European Society for Medical Oncology. 2019;(6):983-989
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BACKGROUND Microseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods. PATIENTS AND METHODS A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method. RESULTS Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP. CONCLUSIONS In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer.
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Does a prostate cancer diagnosis affect management of pre-existing diabetes? Results from PCBaSe Sweden: a nationwide cohort study.
Crawley, D, Garmo, H, Rudman, S, Stattin, P, Zethelius, B, Armes, J, Holmberg, L, Adolfsson, J, Van Hemelrijck, M
BMJ open. 2018;(3):e020787
Abstract
OBJECTIVES Both prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are increasingly prevalent conditions, which frequently coexist in men. Here, we set out to specifically examine the impact of a PCa diagnosis and its treatment on T2DM treatment. SETTING This study uses observational data from Prostate Cancer database Sweden Traject. PARTICIPANTS The study was undertaken in a cohort of 16 778 men with T2DM, of whom 962 were diagnosed with PCa during mean follow-up of 2.5 years. PRIMARY AND SECONDARY OUTCOME MEASURES We investigated the association between PCa diagnosis and escalation in T2DM treatment in this cohort. A treatment escalation was defined as a new or change in anti-T2DM prescription, as recorded in the prescribed drug register (ie, change from diet to metformin or sulphonylurea or insulin). We also investigated how PCa diagnosis was associated with two treatment escalations. Multivariate Cox proportional hazards regression with age as a time scale was used while adjusting for educational level and initial T2DM treatment. RESULTS We found no association between PCa diagnosis and risk of a single treatment escalation (HR 0.99, 95% CI 0.87 to 1.13). However, PCa diagnosis was associated with an increased risk of receiving two consecutive T2DM treatment escalations (HR 1.75, 95% CI 1.38 to 2.22). This increase was strongest for men on gonadotropin-releasing hormone (GnRH) agonists (HR 3.08, 95% CI 2.14 to 4.40). The corresponding HR for men with PCa not on hormonal treatment was 1.40 (95% CI 1.03 to 1.92) and for men with PCa on antiandrogens 0.91 (95% CI 0.29 to 2.82). CONCLUSIONS Men with T2DM who are diagnosed with PCa, particularly those treated with GnRH agonists, were more likely to have two consecutive escalations in T2DM treatment. This suggests a need for closer monitoring of men with both PCa and T2DM, as coexistence of PCa and its subsequent treatments could potentially worsen T2DM control.
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[Low dose rate brachytherapy in low and middle risk prostate cancer: Results and impact on quality of life with 5 year follow up.].
Balbontín, F, Pizzi, P, Canals, A, Alliende, I
Archivos espanoles de urologia. 2017;(10):824-832
Abstract
Low dose rate brachytherapy (LDR-Br) with radioactive isotopes is a curative treatment and has shown to be comparable for the management of localized prostate cancer (PCa) to more conventional treatments such as radical prostatectomy or external beam radiotherapy, but with fewer side effects. The aim of this study is to show the global, specific and biochemical recurrence-free survival in 193 patients undergoing low dose rate Brachytherapy with permanent implants with iodine 125 and analyze the quality of life impact. 193 patients with localized PCa were consecutively treated over a period of 10 years (2005-2015). All of them were followed up on levels of prostate specific antigen (PSA) and 68 of them completed a quality of life survey. The average age was 62.8 years and the average PSA was 6.4 ng/dl at the time of Br. 29.5% of patients were classified as intermediate risk, with a Gleason score sum of 7 and/or a PSA between 10 and 20 ng/dl. Mean follow-up was 64.2 months; overall, specific and biochemical recurrence-free survival were 92.8%, 99.0% and 90.2% respectively. The most significant changes in the quality of life recorded were urinary incontinence, urinary and bowel irritative symptoms, in the first 6 months after brachytherapy. Sexual function shows significant changes but all with favorable response using phosphodiesterase inhibitors. This series of patients with PCa shows similar biochemical free survival rates BFSR in low risk patients to external beam radiotherapy and radical prostatectomy, but better BFSR in intermediate risk patients. The impact in the quality of life was significant in urinary incontinence, urinary irritate symptoms, and sexual function, but they were transitory with the exception of sexual function.
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In prostate cancer, low adiponectin levels are not associated with insulin resistance.
Michalakis, K, Venihaki, M, Mantzoros, C, Vazaiou, A, Ilias, I, Gryparis, A, Margioris, AN
European journal of clinical investigation. 2015;(6):572-8
Abstract
PURPOSE Adiponectin, an adipose tissue-derived hormone with insulin-sensitizing effect, has been inversely associated with several hormonally dependent malignancies. Prostate cancer is associated with low levels of adiponectin, which have been proposed as an independent risk factor for this malignancy. Aim of this study was to examine whether hypoadiponectinaemia in prostate is associated with insulin resistance. EXPERIMENTAL DESIGN Plasma samples and covariate data in the context of a case-control study of 300 Greek men were evaluated including 75 patients with prostate cancer, 75 patients with benign prostatic hyperplasia (BPH) and 150 age-matched healthy controls. RESULTS Patients with prostate cancer had significantly lower plasma adiponectin levels compared with the other two groups, that is BPH patients and healthy controls (7.4 ± 5 ng/mL vs. 11.5 ± 6.4 ng/mL and 12.8 ± 8 ng/mL, respectively). On the other hand, no statistically significant differences were found between patients with prostate cancer and the other two groups for both HOMA-IR and QUICKI (P-value = 0.551). As expected, in all three groups, the levels of adiponectin correlated negatively with HOMA-IR (rho = -0.214, P-value = 0.006), QUICKI (rho = 0.214, P-value = 0.006) and insulin levels (rho = 0.942, P-value < 0.001). CONCLUSION In spite of what would have been expected from the relevant literature, our data suggest that the hypoadiponectinaemia in prostatic cancer does not appear to be associated with insulin resistance.
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The metabolic syndrome and its components in patients with prostate cancer on androgen deprivation therapy.
Morote, J, Gómez-Caamaño, A, Alvarez-Ossorio, JL, Pesqueira, D, Tabernero, A, Gómez Veiga, F, Lorente, JA, Porras, M, Lobato, JJ, Ribal, MJ, et al
The Journal of urology. 2015;(6):1963-9
Abstract
PURPOSE Androgen deprivation therapy may promote the development of the metabolic syndrome in patients with prostate cancer. We assessed the prevalence of the full metabolic syndrome and its components during the first year of androgen deprivation therapy. MATERIALS AND METHODS This observational, multicenter, prospective study included 539 patients with prostate cancer scheduled to receive 3-month depot luteinizing hormone-releasing hormone analogs for more than 12 months. Waist circumference, body mass index, lipid profile, blood pressure and fasting glucose were evaluated at baseline and after 6 and 12 months. The metabolic syndrome was assessed according to NCEP ATP III criteria (2001) and 4 other definitions (WHO 1998, AACE 2003, AHA/NHLBI 2005 and IDF 2005). RESULTS At 6 and 12 months after the initiation of androgen deprivation therapy, significant increases were observed in waist circumference, body mass index, fasting glucose, triglycerides, total cholesterol, and high-density and low-density lipoprotein cholesterol. No significant changes in blood pressure 130/85 or greater were detected. A nonsignificant increase of 3.9% in the prevalence of the full metabolic syndrome (ATP III) was observed (22.9% at baseline vs 25.5% and 26.8% at 6 and 12 months, respectively). The prevalence of the metabolic syndrome at baseline varied according to the definition used, ranging from 9.4% (WHO) to 50% (IDF). At 12 months significant increases in prevalence were observed with the WHO (4.1%) and AHA/NHLBI (8.1%) definitions. CONCLUSIONS Androgen deprivation therapy produces significant early effects on waist circumference, body mass index, fasting glucose, triglycerides and cholesterol. The prevalence of and increase in the metabolic syndrome depend on the defining criteria. Counseling patients on the prevention, early detection and treatment of specific metabolic alterations is recommended.
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[Prostate cancer treated with androgen deprivation therapy: Care and monitoring in daily practice].
Hennequin, C, Bruyère, F, Sedefdjian, A, Bourouina, R, Rouprêt, M
Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie. 2015;(16):1132-9
Abstract
OBJECTIVE Our purpose was to identify measures implemented by urologists and radiation oncologists at the initiation of a 6-month formulation of luteinizing hormone releasing hormone (LHRH) agonist in patients with advanced PCa. MATERIAL This cross-sectional cohort survey was conducted during 6 months. Participants completed a questionnaire of 15 items on the first prescription of an androgen deprivation therapy (ADT), the parameters prescribed for monitoring and information provided to patients. RESULTS The median age of the 1100 enrolled patients was 75 years (range: 51-98 years); 245 patients (29.0%) were metastatic and 411 (39.4%) had a Gleason score ≥ 8. Prior to the treatment initiation, the dosage of the total testosterone was not very often performed (4.8%). Associated comorbidities such as arterial hypertension (53.6%) and hypercholesterolemia (31.8%) did not constitute a barrier to the initiation of ADT, alone (60.5%) or combined with anti-androgens (61%). According to the recommendations of the French Association of Urology (AFU), fasting glycemia was required in 427 patients (41.1%), lipid profile in 380 (36.1%), a blood count in 219 (21.1%) and bone densitometry in 111 (10.8%). The advice given to patients involved diet and lifestyle rules (61%). The potential risks of adverse events (AEs) mentioned were mainly hot flashes (95.5%). CONCLUSION Some recommendations seem insufficiently followed by the French specialists on information and monitoring procedures of ADT, especially in the cardiovascular field.
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Pigmentation-related phenotypes and risk of prostate cancer.
Weinstein, SJ, Virtamo, J, Albanes, D
British journal of cancer. 2013;(3):747-50
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BACKGROUND Solar ultraviolet radiation exposure has been inversely related to prostate cancer incidence and mortality, possibly mediated through vitamin D status. Pigmentation-related traits influence endogenous vitamin D synthesis and may alter risk of prostate cancer. METHODS We examined prostate cancer in relation to hair and eye colour, and skin phototype in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Incident cancer was diagnosed in 1982 out of 20 863 men. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazards models. RESULTS Prostate cancer risk did not differ by eye colour or skin phototype. Men with naturally red hair were significantly less likely to develop prostate cancer (HR=0.46, 95% CI 0.24-0.89) than men with light brown hair (reference). CONCLUSION The red hair phenotype, which results from polymorphisms in the melanocortin-1-receptor (MC1R) gene, is associated with lower risk of prostate cancer. This pigmentation-related trait may influence prostate cancer development either directly, through genetic effects or regulatory mechanisms related to MC1R, another nearby gene, or other pigmentation genes, or indirectly, through associations with other exposures such as sunlight or vitamin D status.