Dietary lipids and environmental xenobiotics as risk factors for prostate cancer: The role of cytochrome P450

Prostate cancer is characterized by high morbidity and mortality rates. According to the World Health Organization data, 1.2 million cases of the disease and 358,000 deaths because of prostate cancer were recorded in 2018. This nosology takes the second place in the structure of oncological morbidity, and the sixth place in the structure of cancer-associated mortality. A large number of works have been devoted to the study of the etiopathogenesis of prostate cancer. In this review, we attempted to summarize some of the results of studies of risk factors for this disease. The article analyzes the results of studies on the possible impact on the development of the disease of both biological factors (age, race, the presence of certain genetic polymorphisms), and lifestyle-related factors (nutrition, obesity, alcohol use, smoking). Despite the urgency of the problem and the huge number of studies conducted, up to date, only for a number of unmodifiable factors, such as age, race, heredity, their unconditional role in the development of prostate cancer have proved. There is no clarity regarding the significance of the role of modifiable, factors, including behavioral, in the development of the disease. The data from the studies are contradictory and not very convincing. Further research in this direction is necessary to get information about the contribution of potential risk factors to the etiopathogenesis of prostate cancer.

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The RADICAL-PC trial.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.178 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 178-178

Author(s):

Jehonathan H Pinthus ◽

Laurence Klotz ◽

Himanshu Lukka ◽

Wilhelmina CM Duivenvoorden ◽

Shirley Pettit ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Cardiovascular Disease ◽

High Risk ◽

Primary Outcome ◽

Intervention Group ◽

Preventive Strategies ◽

Lifestyle Risk Factors ◽

Lifestyle Risk

178 Background: Cardiovascular disease (CVD) occurs frequently in men with prostate cancer (PC), but the reasons are unclear. Specifically, the role of androgen deprivation therapy (ADT) in promoting CVD remains uncertain. There is a lack of evidence to inform preventive strategies against CVD in this high risk group. It is unknown if the evidence to support CVD preventive strategies in the general population can be validly extrapolated to men with PC. Methods: RADICAL-PC combines two prospective studies, one of which is embedded in the other. The Role of Androgen Deprivation Therapy in Cardiovascular Disease – A Longitudinal Prostate Cancer Study (RADICAL PC1) is a prospective cohort study of men within one year of their first diagnosis of PC, or who are within one month of commencing ADT for the first time. Its goal is to identify factors associated with the development of CVD among men with PC, with a particular focus on ADT. The Randomized Intervention for Cardiovascular and Lifestyle Risk Factors in Prostate Cancer Patients (RADICAL PC2) is a randomized, controlled trial embedded in RADICAL PC1. RADICAL PC2 will test a systematic approach to modifying CV and lifestyle risk factors. The intervention group will receive: 1) Standardized advice on healthy diet and exercise; 2) Low-dose antiplatelet agent; 3) Low- to moderate-dose statin; and 4) ACE-I for baseline systolic blood pressure ≥ 130mmHg. Results: The study has been recently funded by Movember clinical trial program of Prostate Cancer Canada, and is launched across Canada. The primary outcome is the occurrence of the composite of cardiovascular death, myocardial infarction, stroke, heart failure, or arterial revascularization. For RADICAL-PC1, 6000 participants will have 90% power to detect a hazard ratio 0.86 for a given exposure. For RADICAL-PC2, 4116 participants randomized, with 434 primary outcome events will have 85% power to detect a hazard ratio of 0.75 in the intervention group. Conclusions: RADICAL PC will be one of the largest prospective studies of CVD – the main competing risk – in men with PC. It will clarify the determinants of CVD in these men, the role of ADT in CVD, and will simultaneously test an intervention to lower the CVD risk in this high-risk population.

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Oncoguía de cáncer de próstata 2020

Latin american journal of clinical sciences and medical technology ◽

10.34141/ljcs9779026 ◽

2020 ◽

Vol 2 (2) ◽

pp. 157-163

Author(s):

Miguel Ángel Jiménez Ríos ◽

Anna Scavuzzo ◽

Diego Antonio Preciado Estrella

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Treatment Guidelines ◽

Digital Rectal Examination ◽

Treatment Monitoring ◽

Grading System ◽

Imaging Diagnosis ◽

Gleason Grading ◽

Cáncer De Próstata

In Mexico, prostate cancer is the first cause of death in men. Instituto Nacional de Cancerología has developed health-care protocols for the main neoplasms. Members of its Urology Department framed Oncoguía de cáncer de próstata 2020, based on a bibliographic revision and a consensus they conducted. It includes the analysis of the risk factors and the central diagnostic elements: specific prostatic antigen (SPA), digital rectal examination (DRE), imaging diagnosis, biopsy, and Gleason grading system. Oncoguía also contains the role of the clinical assessment and life expectancy as treatment guidelines, which, according to the case, are radical prostatectomy, lymph-node treatment, hormone blockade, and treatment monitoring.

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Prognostic role of docetaxel-induced reduction of free testosterone serum levels in metastatic prostate cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.144 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 144-144

Author(s):

Paula Kappler ◽

Stefan Brunotte ◽

Philipp Ivanyi ◽

Michael A. Morgan ◽

Christoph W. Reuter

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Cox Regression ◽

Specific Antigen ◽

Serum Levels ◽

Prognostic Role ◽

Cycle Number ◽

Prognostic Risk Factors ◽

The Impact

144 Background: We have recently demonstrated that a salvage therapy with carboplatin plus weekly docetaxel is effective in docetaxel-refractory prostate cancer (PC) and interferes with testosterone biosynthesis (Reuter et al.; Oncol Res & Treat. 2018, 41 (suppl.1): p.10). In this study, the impact of docetaxel monotherapy on free and total testosterone serum levels (fT, TT) and the prognostic role of fT and TT were analyzed in mPC patients. Methods: 62 consecutive mPC patients were treated with at least two cycles of docetaxel (75 mg/m2 q3w; 50 mg/m2 q2w, or 35 mg/m2 q1w) until disease progression, occurrence of intolerable adverse effects or completion of the planned cycle number. Efficacy measures were done following PCWG2 recommendations. FT and TT were measured before and during chemotherapy. Results: At the current analysis (August 31, 2020), the median follow-up time was 21.2 months. Response of prostate-specific antigen (PSAR; ≥50% PSA reduction) was observed in 42/62 (67.7%) and 12/36 (33.3%) patients with measurable disease exhibited a partial remission (PR). Median progression-free survival (PFS) for all patients was 8.1 months (CI 95% 3.6, 12.5) and median overall survival (OS) was 25.7 months (CI 95% 19.4, 32.1). The most common reversible grade 3/4 toxicity was leukopenia/neutropenia (29/33.9%). Median fT and TT serum levels were reduced below the detection limit during docetaxel treatment (fT: from 0.34 pg/mL to < 0.01 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified PSAR > 50%, fT reduction of 100% and number of organs involved as independent prognostic risk factors for PFS. Furthermore, fT reduction of 100% and FT nadir values < 0.01 pg/mL were independent prognostic risk factors for OS (p < 0.05). Conclusions: These data demonstrate that fT is an important prognostic factor for PFS and OS in mPC patients.

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Prostate cancer in Pennsylvania: The role of older age at diagnosis, aggressiveness, and environmental risk factors on treatment and mortality using data from the Pennsylvania Cancer Registry

Cancer Medicine ◽

10.1002/cam4.3003 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3623-3633

Author(s):

Shirley M. Bluethmann ◽

Ming Wang ◽

Emily Wasserman ◽

Chixiang Chen ◽

Nicholas G. Zaorsky ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Cancer Registry ◽

Environmental Risk ◽

Environmental Risk Factors ◽

Older Age ◽

Age At Diagnosis ◽

Using Data

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Genetic predisposition to prostate cancer: an update

Familial Cancer ◽

10.1007/s10689-021-00227-3 ◽

2021 ◽

Author(s):

Holly Ni Raghallaigh ◽

Rosalind Eeles

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Genetic Variation ◽

High Risk ◽

Cancer Risk ◽

Prostate Cancer Screening ◽

Prostate Cancer Risk ◽

Targeted Screening ◽

European Populations

AbstractImprovements in DNA sequencing technology and discoveries made by large scale genome-wide association studies have led to enormous insight into the role of genetic variation in prostate cancer risk. High-risk prostate cancer risk predisposition genes exist in addition to common germline variants conferring low-moderate risk, which together account for over a third of familial prostate cancer risk. Identifying men with additional risk factors such as genetic variants or a positive family history is of clinical importance, as men with such risk factors have a higher incidence of prostate cancer with some evidence to suggest diagnosis at a younger age and poorer outcomes. The medical community remains in disagreement on the benefits of a population prostate cancer screening programme reliant on PSA testing. A reduction in mortality has been demonstrated in many studies, but at the cost of significant amounts of overdiagnosis and overtreatment. Developing targeted screening strategies for high-risk men is currently the subject of investigation in a number of prospective studies. At present, approximately 38% of the familial risk of PrCa can be explained based on published SNPs, with men in the top 1% of the risk profile having a 5.71-fold increase in risk of developing cancer compared with controls. With approximately 170 prostate cancer susceptibility loci now identified in European populations, there is scope to explore the clinical utility of genetic testing and genetic-risk scores in prostate cancer screening and risk stratification, with such data in non-European populations eagerly awaited. This review will focus on both the rare and common germline genetic variation involved in hereditary and familial prostate cancer, and discuss ongoing research in exploring the role of targeted screening in this high-risk group of men.

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