scholarly journals Linking obesogenic dysregulation to prostate cancer progression

2015 ◽  
Vol 4 (4) ◽  
pp. R68-R80 ◽  
Author(s):  
Renea A Taylor ◽  
Jennifer Lo ◽  
Natasha Ascui ◽  
Matthew J Watt
Keyword(s):  
Prostate Cancer ◽  
Adipose Tissue ◽  
Cancer Progression ◽  
Prostate Gland ◽  
The Body ◽  
Endocrine Function ◽  
Low Grade ◽  
Prostate Cancer Progression ◽  
Cancer Aggressiveness ◽  
Increased Risk

The global epidemic of obesity is closely linked to the development of serious co-morbidities, including many forms of cancer. Epidemiological evidence consistently shows that obesity is associated with a similar or mildly increased incidence of prostate cancer but, more prominently, an increased risk for aggressive prostate cancer and prostate cancer-specific mortality. Studies in mice demonstrate that obesity induced by high-fat feeding increases prostate cancer progression; however, the mechanisms underpinning this relationship remain incompletely understood. Adipose tissue expansion in obesity leads to local tissue dysfunction and is associated with low-grade inflammation, alterations in endocrine function and changes in lipolysis that result in increased delivery of fatty acids to tissues of the body. The human prostate gland is covered anteriorly by the prominent peri-prostatic adipose tissue and laterally by smaller adipose tissue depots that lie directly adjacent to the prostatic surface. We discuss how the close association between dysfunctional adipose tissue and prostate epithelial cells might result in bi-directional communication to cause increased prostate cancer aggressiveness and progression. However, the literature indicates that several ‘mainstream’ hypotheses regarding obesity-related drivers of prostate cancer progression are not yet supported by a solid evidence base and, in particular, are not supported by experiments using human tissue. Understanding the links between obesity and prostate cancer will have major implications for the health policy for men with prostate cancer and the development of new therapeutic or preventative strategies.

scholarly journals Alterations in chromosome spatial compartmentalization classify prostate cancer progression

2021 ◽  
Author(s):  
Rebeca San Martin ◽  
Priyojit Das ◽  
Renata Dos Reis Marques ◽  
Yang Xu ◽  
Rachel Patton McCord
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
3D Structure ◽  
Gene Clusters ◽  
Metastatic Potential ◽  
Chromosome 21 ◽  
Prostate Cancer Progression ◽  
Normal Epithelium ◽  
Chromosome Conformation ◽  
Cancer Aggressiveness

Prostate cancer aggressiveness and metastatic potential are influenced by gene expression, genomic aberrations, and cellular morphology. These processes are in turn dependent in part on the 3D structure of chromosomes, packaged inside the nucleus. Using chromosome conformation capture (Hi-C), we conducted a systematic genome architecture comparison on a cohort of cell lines that model prostate cancer progression, ranging from normal epithelium to bone metastasis. Here, we describe how chromatin compartmentalization identity (A- open vs. B-closed) changes with progression: specifically, we find that 48 gene clusters switch from the B to the A compartment, including androgen receptor, WNT5A, and CDK14. These switches could prelude transcription activation and are accompanied by changes in the structure, size, and boundaries of the topologically associating domains (TADs). Further, compartmentalization changes in chromosome 21 are exacerbated with progression and may explain, in part, the genesis of the TMPRSS2-ERG translocation: one of the main drivers of prostate cancer.  These results suggest that discrete, 3D genome structure changes play a deleterious role in prostate cancer progression. 

Association between air cadmium exposure and prostate cancer aggressiveness at diagnosis

2020 ◽  
Author(s):  
Vishwaarth Vijayakumar ◽  
Michael R. Abern ◽  
Jyotsna S. Jagai ◽  
André Kajdacsy-Balla
Keyword(s):  
Prostate Cancer ◽  
General Population ◽  
Cancer Progression ◽  
Cadmium Exposure ◽  
Study Cohort ◽  
Low Grade ◽  
Gleason Grade ◽  
County Level ◽  
Ambient Exposure ◽  
Cancer Aggressiveness

Abstract Background There is conflicting evidence of a relationship between cadmium exposure and prostate cancer (PC) mortality in the general population. Since most PCs are indolent and clinically inconsequential, low grade and low stage tumors may mask an association between cadmium exposure and PC mortality. Methods We collected patient data from the 2010 – 2014 Surveillance, Epidemiology, and End Results (SEER). Aggressiveness at diagnosis was defined as stage categorized as either metastatic or localized and Gleason grade as high or low. The 2011 National Air Toxics Assessment database provided county-level air cadmium concentrations. We assessed the association between ambient exposure to air cadmium and PC aggressiveness at diagnosis in the US. Odds Ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression comparing the 80 th to 20 th percentile of cadmium exposure and adjusted for age at diagnosis, sociodemographic status, smoking prevalence and overall air quality at the county-level and were stratified by race and degree of urbanization by Rural-Urban Continuum Codes (RUCC). Similar OR and CI were calculated for arsenic and lead since exposure to these metals sometimes coincide with cadmium exposure as well. Results The study cohort consisted of 230,540 cases from 493 counties. Higher air cadmium exposure was associated with an increased likelihood of metastatic PC compared to localized PC (OR 1.02, CI 1.01 – 1.03) and higher Gleason grade at diagnosis (OR 1.01, CI 1.00 – 1.02). The strongest associations were observed in nonmetropolitan areas with urban populations of 20,000 to 250,000 (RUCC2 counties): (OR 1.26, CI 1.14 – 1.39) for metastatic vs. localized PC, and (OR 1.36, CI 1.25 – 1.49) for high vs . low grade cases although these results differed somewhat by race. Compared to arsenic and lead, cadmium tended to show stronger associations with PC aggressiveness. Conclusion The strongest associations between air cadmium exposure and tumor aggressiveness were found among RUCC 2 counties, areas where 40 million Americans reside. Further studies are necessary to identify air cadmium pollution sources in these communities and to rule out additional confounding factors. Air cadmium exposure in the general population may be a more important factor than previously recognized in prostate cancer progression.

scholarly journals High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
David P. Labbé ◽  
Giorgia Zadra ◽  
Meng Yang ◽  
Jaime M. Reyes ◽  
Charles Y. Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
High Fat Diet ◽  
Cellular Proliferation ◽  
Saturated Fat ◽  
Prostate Cancer Progression ◽  
Transcriptional Program ◽  
High Fat ◽  
Metabolic Alterations ◽  
Increased Risk

Abstract Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet.

scholarly journals Promoter Methylation in APC, RUNX3, and GSTP1 and Mortality in Prostate Cancer Patients

2009 ◽  
Vol 27 (19) ◽  
pp. 3161-3168 ◽  
Author(s):  
Lorenzo Richiardi ◽  
Valentina Fiano ◽  
Loredana Vizzini ◽  
Laura De Marco ◽  
Luisa Delsedime ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Promoter Methylation ◽  
A Priori ◽  
Methylation Status ◽  
Specific Antigen ◽  
Prostate Cancer Progression ◽  
Increased Risk ◽  
In The Beginning

Purpose There is a need to better understand prostate cancer progression and identify new prognostic markers for this tumor. We investigated the association between promoter methylation in a priori selected genes and survival in two independent large series of prostate cancer patients. Methods We followed up with two cohorts of patients (216 patients diagnosed in 1982 to 1988 and 243 patients diagnosed in 1993 to 1996) diagnosed at one hospital pathology ward in Turin, Italy. DNA was obtained from paraffin-embedded tumor tissues and evaluated for promoter methylation status in glutathione S-transferase (GSTP1), adenomatous polyposis coli (APC), and runt-related transcription factor 3 (RUNX3). Results The two cohorts had different prevalences of methylation in APC (P = .047), GSTP1 (P = .002), and RUNX3 (P < .001). Methylation in APC was associated with an increased risk of prostate cancer–specific mortality (hazard ratio [HR] = 1.42; 95% CI, 0.98 to 2.07 in the 1980s cohort; HR = 1.57; 95% CI, 0.95 to 2.62 in the 1990s cohort; HR = 1.49; 95% CI, 1.11 to 2.00 in the two cohorts combined). In subgroup analyses, the HRs were higher among patients with a Gleason score less than 8 (HR = 1.52; 95% CI, 0.85 to 2.73 in the 1980s cohort; HR = 2.09; 95% CI, 1.02 to 4.28 in the 1990s cohort). Methylation in RUNX3 was associated with prostate cancer mortality only in the 1990s cohort, and methylation in GSTP1 did not predict mortality in either cohort. Conclusion The pattern of hypermethylation may have changed after the introduction of prostate-specific antigen testing in the beginning of the 1990s. Promoter methylation in APC was identified as a marker for prostate cancer progression.

scholarly journals High B7‐H3 expression is linked to increased risk of prostate cancer progression

2020 ◽  
Vol 70 (10) ◽  
pp. 733-742 ◽  
Author(s):  
Sarah Bonk ◽  
Pinar Tasdelen ◽  
Martina Kluth ◽  
Claudia Hube‐Magg ◽  
Georgia Makrypidi‐Fraune ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Increased Risk

scholarly journals Genetic Analysis Reveals a Significant Contribution of CES1 to Prostate Cancer Progression in Taiwanese Men

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1346
Author(s):  
Chien-Chih Ke ◽  
Lih-Chyang Chen ◽  
Chia-Cheng Yu ◽  
Wei-Chung Cheng ◽  
Chao-Yuan Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Meta Analysis ◽  
Cholesterol Homeostasis ◽  
Nucleotide Polymorphisms ◽  
Prostate Cancer Progression ◽  
Multiple Test Correction ◽  
Multiple Test ◽  
Cancer Aggressiveness

The genes that influence prostate cancer progression remain largely unknown. Since the carboxylesterase gene family plays a crucial role in xenobiotic metabolism and lipid/cholesterol homeostasis, we hypothesize that genetic variants in carboxylesterase genes may influence clinical outcomes for prostate cancer patients. A total of 478 (36 genotyped and 442 imputed) single nucleotide polymorphisms (SNPs) in five genes of the carboxylesterase family were assessed in terms of their associations with biochemical recurrence (BCR)-free survival in 643 Taiwanese patients with prostate cancer who underwent radical prostatectomy. The strongest association signal was shown in CES1 (P = 9.64 × 10−4 for genotyped SNP rs8192935 and P = 8.96 × 10−5 for imputed SNP rs8192950). After multiple test correction and adjustment for clinical covariates, CES1 rs8192935 (P = 9.67 × 10−4) and rs8192950 (P = 9.34 × 10−5) remained significant. These SNPs were correlated with CES1 expression levels, which in turn were associated with prostate cancer aggressiveness. Furthermore, our meta-analysis, including eight studies, indicated that a high CES1 expression predicted better outcomes among prostate cancer patients (hazard ratio 0.82, 95% confidence interval 0.70–0.97, P = 0.02). In conclusion, our findings suggest that CES1 rs8192935 and rs8192950 are associated with BCR and that CES1 plays a tumor suppressive role in prostate cancer.

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