Role of Precision Oncology in Type II Endometrial and Prostate Cancers in the African Population: Global Cancer Genomics Disparities

Precision oncology can be defined as molecular profiling of tumors to identify targetable alterations. Emerging research reports the high mortality rates associated with type II endometrial cancer in black women and with prostate cancer in men of African ancestry. The lack of adequate genetic reference information from the African genome is one of the major obstacles in exploring the benefits of precision oncology in the African context. Whilst external factors such as the geography, environment, health-care access and socio-economic status may contribute greatly towards the disparities observed in type II endometrial and prostate cancers in black populations compared to Caucasians, the contribution of African ancestry to the contribution of genetics to the etiology of these cancers cannot be ignored. Non-coding RNAs (ncRNAs) continue to emerge as important regulators of gene expression and the key molecular pathways involved in tumorigenesis. Particular attention is focused on activated/repressed genes and associated pathways, while the redundant pathways (pathways that have the same outcome or activate the same downstream effectors) are often ignored. However, comprehensive evidence to understand the relationship between type II endometrial cancer, prostate cancer and African ancestry remains poorly understood. The sub-Saharan African (SSA) region has both the highest incidence and mortality of both type II endometrial and prostate cancers. Understanding how the entire transcriptomic landscape of these two reproductive cancers is regulated by ncRNAs in an African cohort may help elucidate the relationship between race and pathological disparities of these two diseases. This review focuses on global disparities in medicine, PCa and ECa. The role of precision oncology in PCa and ECa in the African population will also be discussed.

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The Role of C-Reactive Protein in Kidney, Bladder, and Prostate Cancers

Frontiers in Immunology ◽

10.3389/fimmu.2021.721989 ◽

2021 ◽

Vol 12 ◽

Author(s):

Daniel O’Brian ◽

Megan Prunty ◽

Alexander Hill ◽

Jonathan Shoag

Keyword(s):

Prostate Cancer ◽

Advanced Disease ◽

Definitive Treatment ◽

C Reactive Protein ◽

Cancer Specific Survival ◽

Reactive Protein ◽

Cancer Pathogenesis ◽

Prostate Cancers ◽

The Relationship

C-Reactive Protein (CRP) is associated with diverse outcomes in patients with, or suspected to have, genitourinary malignancies. CRP levels have been shown to be associated with the probability of a prostate cancer diagnosis in patients with elevated PSA, the probability of biochemical recurrence following definitive treatment for localized prostate cancer, and decreased overall survival for patients with advanced disease. In patients with bladder and kidney cancers, CRP levels have been associated with disease progression, stage, and cancer-specific survival. Despite the abundance of correlative studies, the relationship between CRP levels and genitourinary cancer pathogenesis is not clearly understood. Here, we review the evidence for CRP as a biomarker in genitourinary (GU) cancers, with specific focus on potential clinical applications.

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Inhibición de Crecimiento de Tumores de Cáncer de Próstata en Hipertermia Magnética mediada por Nanopartículas en Estudios Preclínicos: una Revisión de Alcance

10.24254/cnib.21.26 ◽

2021 ◽

Author(s):

◽

J. A. Parada Peralta

Keyword(s):

Prostate Cancer ◽

Tumor Growth ◽

Magnetic Nanoparticle ◽

Magnetic Hyperthermia ◽

Tumor Growth Inhibition ◽

Tissue Penetration ◽

Deep Tissue ◽

Incidence And Mortality ◽

Low Toxicity ◽

The Relationship

Prostate Cancer is one of the major concern types of cancer among men with respect to incidence and mortality. One relatively recent therapy against it, provided by Nanomedicine, is Nanoparticle mediated Magnetic Hyperthermia, which consists on tumor heating when exposed to an Alternating Magnetic Field in order to inhibit tumor growth (around 42 °C) (and make tumor sensible to other therapies: synergia) or to cause cancer cell apoptosis (greater temperature than 42°C). This procedure has several advantages like deep-tissue-penetration, targeted heating, low toxicity by Nanoparticles, and others. To this treatment, some of the Magnetic Nanoparticle properties are fundamental to its success, principaly the size, morphology, etc. Here, therefore, the relationship between the size of the employed Nanoparticles and the Tumor Growth Inhibition that cause is reviewed when treating Prostate Cancer tumors on mice models by Magnetic Hyperthermia.

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SOX9 stands for a bio-marker for prostate cancer detection

10.21203/rs.3.rs-53227/v1 ◽

2020 ◽

Author(s):

Hao Zi ◽

Wen-Lin Tao ◽

Lei Gao ◽

Zhao-Hua Yu ◽

Xiao-Dong Bai ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Detection ◽

Roc Curve ◽

Operating Characteristic ◽

Diagnostic Value ◽

Quantitative Real Time Pcr ◽

Optimal Cutoff ◽

Qrt Pcr ◽

Incidence And Mortality ◽

The Relationship

Abstract Background Prostate cancer is one of common cancers around the world, and in our country the incidence and mortality of PCa are both increasing. More and more reports have revealed that SOX9 is involved in various human cancers. In this study, we aimed to explore the relationship between SOX9 expression and diagnostic value of PCa patients. Methods In this study, quantitative real-time PCR (qRT-PCR) was performed to determine the expression of SOX9 of the 131 PCa patients and 74 healthy volunteers. And receiver operating characteristic (ROC) curve was used to determine the diagnostic value of SOX9 for PCa patients. Results The results of qRT-PCR showed that the expression of serum SOX9 in PCa patients was higher than that in healthy controls (P < 0.05). And the expression of SOX9 was significantly associated with PSA (P = 0.001), differentiation (P = 0.000), and lymph node metastasis (P = 0.000). Besides, the area under the ROC curve (AUC) was 0.966 with the sensitivity of 93.2% and specificity of 87.8% respectively. The optimal cutoff value of SOX9 was 2.34. Conclusions Our results found that SOX9 is a novel oncogene for PCa, and may be a novel and effective biomarker for the diagnosis of patients with PCa.

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Possible role of Thiazolidinedione in the management of Type-II Endometrial Cancer

Medical Hypotheses ◽

10.1016/j.mehy.2019.03.014 ◽

2019 ◽

Vol 126 ◽

pp. 78-81

Author(s):

Kusuma Kumari Garikapati ◽

V.V.V. Ravi Kiran Ammu ◽

Praveen T. Krishnamurthy ◽

Pavan Kumar Chintamaneni ◽

Sai kiran S.S. Pindiprolu

Keyword(s):

Endometrial Cancer ◽

Type Ii

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Epidemiology of prostate cancer

10.1093/med/9780199659579.003.0058 ◽

2017 ◽

Author(s):

Timothy J. Key ◽

Alison J. Price

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Potential Risk ◽

African Ancestry ◽

Prostate Cancer Risk ◽

Positive Association ◽

Incidence Rates ◽

Nutritional Factors ◽

Incidence And Mortality ◽

Potential Risk Factors

Prostate cancer is the second most common malignancy and the sixth most common cause of cancer death for men worldwide. The highest incidence and mortality rates are in populations that originated in Africa, such as African Americans. Rates are also high in Western countries and generally low in East and South Asia. Incidence rates are increasing in some countries which until recently had low rates, but are not changing much in countries which already have high rates. The only well-established risk factors are increasing age, African ancestry, family history of the disease, and certain genetic factors, none of which is modifiable. Many potential risk factors have been investigated in epidemiological studies and randomized trials. Observational studies have shown that prostate cancer risk is positively associated with the plasma concentration of insulin-like growth factor-I, but is not strongly associated with testosterone or other sex hormones. Studies of nutritional factors suggest that risk may be higher in men with a high intake of animal foods and dairy products, but this relationship is not clear enough to be considered as established. Some studies of other nutritional factors such as fat, lycopene and other carotenoids, vitamin D, vitamin E and selenium have suggested possible associations, but overall do not show any clear relationships. Research on other possible risk factors has shown a small positive association of risk with height, but little association with obesity, smoking or alcohol intake, and evidence on sexual behaviour and sexually transmitted infections is inconclusive. Further research is needed, particularly to determine whether potential risk factors may be related more to aggressive than to indolent prostate cancer.

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Growth Modulatory Role of Zinc in Prostate Cancer and Application to Cancer Therapeutics

International Journal of Molecular Sciences ◽

10.3390/ijms21082991 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2991 ◽

Cited By ~ 2

Author(s):

Phuong Kim To ◽

Manh Hung Do ◽

Jin-Hyoung Cho ◽

Chaeyong Jung

Keyword(s):

Prostate Cancer ◽

Mammalian Cells ◽

Tumor Development ◽

Cancer Therapeutics ◽

Underlying Mechanism ◽

Reproductive Organs ◽

Zinc Homeostasis ◽

Prostate Cancer Development ◽

Prostate Cancers

Zinc is a group IIB heavy metal. It is an important regulator of major cell signaling pathways in most mammalian cells, functions as an antioxidant and plays a role in maintaining genomic stability. Zinc deficiency leads to severe diseases in the brain, pancreas, liver, kidneys and reproductive organs. Zinc loss occurs during tumor development in a variety of cancers. The prostate normally contains abundant intracellular zinc and zinc loss is a hallmark of the development of prostate cancer development. The underlying mechanism of this loss is not clearly understood. The knowledge that excess zinc prevents the growth of prostate cancers suggests that zinc-mediated therapeutics could be an effective approach for cancer prevention and treatment, although challenges remain. This review summarizes the specific roles of zinc in several cancer types focusing on prostate cancer. The relationship between prostate cancer and the dysregulation of zinc homeostasis is examined in detail in an effort to understand the role of zinc in prostate cancer.

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Role of splice variants in the metastatic progression of prostate cancer

Biochemical Society Transactions ◽

10.1042/bst20120026 ◽

2012 ◽

Vol 40 (4) ◽

pp. 870-874 ◽

Cited By ~ 16

Author(s):

Rachel M. Hagen ◽

Michael R. Ladomery

Keyword(s):

Prostate Cancer ◽

Cancer Metastasis ◽

Splice Variants ◽

Human Cancer ◽

Metastatic Potential ◽

Metastatic Progression ◽

Cellular Phenotype ◽

Prostate Cancer Metastasis ◽

The Relationship

AS (alternative splicing) and its role in disease, especially cancer, has come to forefront in research over the last few years. Alterations in the ratio of splice variants have been widely observed in cancer. Splice variants of cancer-associated genes have functions that can alter cellular phenotype, ultimately altering metastatic potential. As metastases are the cause of approximately 90% of all human cancer deaths, it is crucial to understand how AS is dysregulated in metastatic disease. We highlight some recent studies into the relationship between altered AS of key genes and the initiation of prostate cancer metastasis.

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The different genetic alterations between Western and Chinese prostate cancers and the underlying mechanisms.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.184 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 184-184

Author(s):

Xueying Mao ◽

Nuria Coll Bastus ◽

Lara Boyd ◽

Yongwei Yu ◽

Guoping Ren ◽

...

Keyword(s):

Prostate Cancer ◽

Genetic Alterations ◽

Cag Repeat ◽

Fluorescence In Situ Hybridisation ◽

Genome Wide ◽

Incidence And Mortality ◽

Geographical Regions ◽

Prostate Cancers ◽

Underlying Mechanisms ◽

Two Populations

184 Background: Prostate cancer shows a wide variation in the clinical incidence and mortality rates of different geographical regions. While it is the most common male cancer in Western countries, it is much less frequent in Asian countries. We investigated genomic changes in prostate cancers from UK and China using microarrays to determine the genetic similarities and differences as well as the underlying mechanisms. Methods: We determined genome-wide genomic alterations using Affymetrix SNP array 6.0, and evaluated data using fluorescence in situ hybridisation (FISH) and immunohistochemistry. In addition, we assess androgen induced TMPRSS2 and ERG co-localization and fusion. Microsatellite analysis was used for AR CAG repeat polymorphism in UK and Chinese population. Results: Genome-wide analysis of 32 UK and 39 Chinese samples revealed that losses of 21q22 (leading to TMPRSS2:ERG fusion) and 10q23.3 (PTEN) were at much higher frequency in Western than Chinese prostate cancers. Using FISH analysis of 160 UK and 143 Chinese samples, we showed that PTEN deletion and ERG rearrangements were at a significantly higher frequency in samples from UK than China (p<0.001 for both). We found that PTEN and ERG protein were also differentially expressed (p<0.001) in the two populations. Investigating this further, we induced TMPRSS2 and ERG gene proximity and TMPRSS2:ERG fusion in two immortalised prostate epithelial cell lines by exposure to high dose of androgen. This androgen treatment did not cause increased global DNA damage but was associated with low expression of PIWIL1, which is involved in repairing double-strand breaks. Overexpression of PIWIL1 by transfection inhibited androgen induced TMPRSS2:ERG fusion. We found that AR CAG repeat lengths, which associated with AR activity, are significantly shorter in the UK than Chinese patients (p<0.05). Conclusions: We revealed genomic differences in prostate cancer comparing the high-risk (Western) and low-risk (Chinese) populations. We further demonstrated that TMPRSS2:ERG fusion can be induced by androgen. The difference of CAG repeat length between the two populations are potentially associated with TMPRSS2:ERG fusion positive prostate cancers.

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Periprostatic venous androgen levels in a subset of patients with prostate cancer: An investigation into a novel role of testosterone in localized prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.341 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 341-341

Author(s):

Lewis Thomas ◽

Mohammad Alyamani ◽

Jianbo Li ◽

Andrei Purysko ◽

Eric A. Klein ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Volume ◽

Venous Blood ◽

Venous Drainage ◽

Increased Risk ◽

Vein Diameter ◽

Clinically Significant ◽

The Relationship ◽

Androgen Levels

341 Background: While androgens drive prostate cancer (PCa), studies of systemic levels in eugonadal patients have not shown a relationship with development or progression of PCa. This study characterizes the relationship between systemic, local venous, and tissue androgen levels to understand the regulation and influence of androgens on localized PCa. Methods: Peripheral & periprostatic venous blood & prostate tissue were collected from patients undergoing radical prostatectomy (RP). Androgen levels (testosterone (T) and dihydrotestosterone (DHT)) were assessed by mass spectrometry. PCa grade and stage, PSA, prostate volume, and periprostatic vein diameter (PPVD) on MRI were recorded. A second cohort of patients undergoing just prostate MRI (non-surgical) was assessed to investigate the relationship between PPVD and disease severity. Results: Samples were collected from 176 patients. Analysis identified a subset of patients with elevated periprostatic T (ppT) relative to systemic T (sT) including 25% with ppT/sT > 2, 14% with ppT/sT > 4, and 7% with ppT/sT > 10. Patients with ppT/sT > 4 had supraphysiologic T levels in the periprostatic venous blood (mean 4223ng/mL). These patients also had higher than predicted levels of tissue T and DHT (tT/sT of 0.48 vs 0.24 (p = 0.004) and tDHT/sT of 7.31 vs 4.72 (p = 0.011)). In the surgical cohort, PPVD was increased in patients with elevated ppT/sT levels (5.8mm vs 3.7mm, p = 0.013). In the biopsy cohort (n = 200), increased PPVD was associated with an increased risk of diagnosis of PCa (4.39mm vs 3.43mm p = 0.006) and clinically significant PCa (4.35mm vs 3.43mm p = 0.01). Conclusions: In a subset of patients with PCa, periprostatic venous T levels were highly elevated compared to peripheral levels. Tissue T and DHT were also increased, and MRI demonstrated increased PPVD. We hypothesize that collateralization of venous drainage from the gonadal vein leads to both high local T and dilated veins. In a biopsy cohort, increased PPVD was associated with an increased risk of diagnosis of any and clinically significant PCa, suggesting that high periprostatic androgen levels may play a role in development of PCa.

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The Role of BRCA Testing in Hereditary Pancreatic and Prostate Cancer Families

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_238977 ◽

2019 ◽

pp. 79-86 ◽

Cited By ~ 11

Author(s):

Robert Pilarski

Keyword(s):

Prostate Cancer ◽

Parp Inhibitors ◽

Gleason Grade ◽

Brca1 And Brca2 ◽

Direct Evaluation ◽

Panel Testing ◽

Post Test ◽

Uncertain Significance ◽

Prostate Cancers

Beyond breast and ovarian cancers, mutations in the BRCA1 and BRCA2 genes increase risks for pancreatic and prostate cancers and contribute to the prevalence of these cancers. Mutations in a number of other genes have also been shown to increase the risk for these cancers as well. Genetic testing is playing an increasingly important role in the treatment of patients with pancreatic and prostate cancer and is now recommended for all patients with pancreatic or metastatic prostate cancer, as well as patients with high Gleason grade prostate cancer and a remarkable family history. Identification of an inherited mutation can direct evaluation of the patient for other cancer risks as well as identification and management of disease in at-risk relatives. Growing evidence suggests improved responses to PARP inhibitors and other therapies in patients with mutations in the BRCA and other DNA repair genes. Although more work must be done to clarify the prevalence and penetrance of mutations in genes other than BRCA1 and BRCA2 in patients with pancreatic and prostate cancer, in most cases, testing is now being done with a panel of multiple genes. Because of the complexities in panel testing and the increased likelihood of finding variants of uncertain significance, pre- and post-test genetic counseling are essential.

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