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de Melo IG, Tavares V, Pereira D, Medeiros R. Contribution of Endothelial Dysfunction to Cancer Susceptibility and Progression: A Comprehensive Narrative Review on the Genetic Risk Component. Curr Issues Mol Biol 2024; 46:4845-4873. [PMID: 38785560 PMCID: PMC11120512 DOI: 10.3390/cimb46050292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 05/09/2024] [Accepted: 05/13/2024] [Indexed: 05/25/2024] Open
Abstract
Venous thromboembolism (VTE) is a challenging clinical obstacle in oncological settings, marked by elevated incidence rates and resulting morbidity and mortality. In the context of cancer-associated thrombosis (CAT), endothelial dysfunction (ED) plays a crucial role in promoting a pro-thrombotic environment as endothelial cells lose their ability to regulate blood flow and coagulation. Moreover, emerging research suggests that this disorder may not only contribute to CAT but also impact tumorigenesis itself. Indeed, a dysfunctional endothelium may promote resistance to therapy and favour tumour progression and dissemination. While extensive research has elucidated the multifaceted mechanisms of ED pathogenesis, the genetic component remains a focal point of investigation. This comprehensive narrative review thus delves into the genetic landscape of ED and its potential ramifications on cancer progression. A thorough examination of genetic variants, specifically polymorphisms, within key genes involved in ED pathogenesis, namely eNOS, EDN1, ACE, AGT, F2, SELP, SELE, VWF, ICAM1, and VCAM1, was conducted. Overall, these polymorphisms seem to play a context-dependent role, exerting both oncogenic and tumour suppressor effects depending on the tumour and other environmental factors. In-depth studies are needed to uncover the mechanisms connecting these DNA variations to the pathogenesis of malignant diseases.
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Affiliation(s)
- Inês Guerra de Melo
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Dep., Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto. CCC), 4200-072 Porto, Portugal; (I.G.d.M.); (V.T.)
- Faculty of Medicine of University of Porto (FMUP), 4200-072 Porto, Portugal
| | - Valéria Tavares
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Dep., Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto. CCC), 4200-072 Porto, Portugal; (I.G.d.M.); (V.T.)
- Faculty of Medicine of University of Porto (FMUP), 4200-072 Porto, Portugal
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
| | - Deolinda Pereira
- Oncology Department, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal;
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Dep., Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto. CCC), 4200-072 Porto, Portugal; (I.G.d.M.); (V.T.)
- Faculty of Medicine of University of Porto (FMUP), 4200-072 Porto, Portugal
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
- Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal
- Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal
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Xiao Y, Dong Z, Zhu J, You J, Fan J. Association between ACE A240T polymorphism and cancer risk: a meta-analysis. J Int Med Res 2019; 47:5917-5925. [PMID: 31694436 PMCID: PMC7045645 DOI: 10.1177/0300060519882559] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Objectives The relationship between the A240T polymorphism in the angiotensin-converting enzyme (ACE) gene and cancer risk remains controversial. Therefore, we conducted a meta-analysis of relevant studies from the published literature. Methods We comprehensively searched available databases to identify eligible studies on the relationship of ACE A240T polymorphism with cancer risk. We calculated pooled odds ratios (OR) with 95% confidence intervals (CI) and then evaluated heterogeneity and publication bias. Results Eight case-control studies were identified from five articles. Results showed that the ACE A240T polymorphism was related to cancer risk (AT vs AA: OR 2.14, 95% CI: 1.51–3.04; TT vs AA: OR 1.07, 95% CI: 0.90–1.27; recessive model: OR 0.48, 95% CI: 0.31–0.77; dominant model: OR 2.13, 95% CI: 1.54–2.97). The same conclusion was made for subgroup analysis by race or cancer type. In the subgroup analysis by quality score assessment, the ACE A240T polymorphism contributed to cancer risk in high-quality studies but not in low-quality studies. Conclusion The A240T polymorphism in the ACE gene might be related to the risk of cancer. Nevertheless, large-scale studies should be performed to obtain convincing evidence on the roles of ACE A240T polymorphism on cancer risk.
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Affiliation(s)
- Yingjun Xiao
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.,Clinical Laboratory, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Zheqing Dong
- Clinical Laboratory, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Ji Zhu
- Clinical Laboratory, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jinbiao You
- Clinical Laboratory, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jun Fan
- State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China
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Wang ZY, Li HY, Jiang ZP, Zhou TB. Relationship between angiotensin-converting enzyme insertion/deletion gene polymorphism and prostate cancer susceptibility. J Cancer Res Ther 2018; 14:S375-S380. [PMID: 29970692 DOI: 10.4103/0973-1482.171366] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND AND OBJECTIVE Investigations on the relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and prostate cancer risk are conflicting. This meta-analysis was conducted to assess the relationship between ACE I/D gene polymorphism and prostate cancer risk. MATERIALS AND METHODS Reports were identified from PubMed, Cochrane Library, and China Biological Medicine (CBM)-disc (CBM database) on December 30, 2014, and eligible studies were recruited. RESULTS ACE I/D gene polymorphism was not associated with prostate cancer risk for overall populations in this meta-analysis (D allele: Odds ratio [OR] =1.56, 95% confidence interval [95% CI]: 1.00-2.46, P = 0.05; DD genotype: OR = 1.74, 95% CI: 0.95-3.20, P = 0.07; II genotype: OR = 0.67, 95% CI: 0.39-1.15, P = 0.15). Furthermore, the association of ACE I/D gene polymorphism with colorectal cancer risk was not found for the Caucasians. Interestingly, ACE I/D gene polymorphism was associated with prostate cancer risk for the Asian population and Latino population. CONCLUSIONS There was an association between ACE I/D gene polymorphism and prostate cancer risk for the Asians and Latino population in this meta-analysis. However, more investigations should be performed to confirm this relationship.
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Affiliation(s)
- Zhong-Yang Wang
- Department of Urology Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Hong-Yan Li
- Department of Nephrology, Huadu District People's Hospital, Southern Medical University, Guangzhou, China
| | - Zong-Pei Jiang
- Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Tian-Biao Zhou
- Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
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Marques D, Ferreira-Costa LR, Ferreira-Costa LL, Correa RDS, Borges AMP, Ito FR, Ramos CCDO, Bortolin RH, Luchessi AD, Ribeiro-dos-Santos Â, Santos S, Silbiger VN. Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features. World J Gastroenterol 2017; 23:6854-6867. [PMID: 29085228 PMCID: PMC5645618 DOI: 10.3748/wjg.v23.i37.6854] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2017] [Revised: 06/24/2017] [Accepted: 08/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the association between 16 insertion-deletions (INDEL) polymorphisms, colorectal cancer (CRC) risk and clinical features in an admixed population.
METHODS One hundred and forty patients with CRC and 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. Clinicopathological data were obtained by consulting the patients’ clinical charts, intra-operative documentation, and pathology scoring.
RESULTS Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis (TNM) stage risk, the Ins alleles of ACE, HLAG and TP53 (6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk.
CONCLUSION The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, HLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.
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Affiliation(s)
- Diego Marques
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Programa de Pós-graduação em Ciências Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66055-080, Pará, Brazil
| | - Layse Raynara Ferreira-Costa
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
| | - Lorenna Larissa Ferreira-Costa
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
| | - Romualdo da Silva Correa
- Departamento de Cirurgia Oncológica, Liga Norte Riograndense Contra o Câncer, Natal 59040-000, Rio Grande do Norte, Brazil
| | - Aline Maciel Pinheiro Borges
- Departamento de Cirurgia Oncológica, Liga Norte Riograndense Contra o Câncer, Natal 59040-000, Rio Grande do Norte, Brazil
| | - Fernanda Ribeiro Ito
- Departamento de Cirurgia Oncológica, Liga Norte Riograndense Contra o Câncer, Natal 59040-000, Rio Grande do Norte, Brazil
| | - Carlos Cesar de Oliveira Ramos
- Laboratório de Patologia e Citopatologia, Liga Norte Riograndense Contra o Câncer, Natal 59040-000, Rio Grande do Norte, Brazil
| | - Raul Hernandes Bortolin
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Programa de Pós-graduação em Ciências Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
| | - André Ducati Luchessi
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Programa de Pós-graduação em Ciências Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
| | - Ândrea Ribeiro-dos-Santos
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66055-080, Pará, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Pará, Brazil
| | - Sidney Santos
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66055-080, Pará, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Pará, Brazil
| | - Vivian Nogueira Silbiger
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Programa de Pós-graduação em Ciências Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
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Wilson C, Leiblich A, Goberdhan DCI, Hamdy F. The Drosophila Accessory Gland as a Model for Prostate Cancer and Other Pathologies. Curr Top Dev Biol 2016; 121:339-375. [PMID: 28057306 PMCID: PMC5224695 DOI: 10.1016/bs.ctdb.2016.06.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The human prostate is a gland of the male reproductive tract, which together with the seminal vesicles, is responsible for most seminal fluid production. It is a common site of cancer, and unlike other glands, it typically enlarges in aging men. In flies, the male accessory glands make many major seminal fluid components. Like their human equivalents, they secrete proteins from several conserved families, including proteases, lectins, and cysteine-rich secretory proteins, some of which interact with sperm and affect fertility. A key protein, sex peptide, is not conserved in vertebrates but plays a central role in mediating long-term effects on females after mating. Although postmitotic, one epithelial cell type in the accessory glands, the secondary cell, continues to grow in adults. It secretes microvesicles called exosomes from the endosomal multivesicular body, which, after mating, fuse with sperm. They also appear to affect female postmating behavior. Remarkably, the human prostate epithelium also secretes exosomes, which fuse to sperm in vitro to modulate their activity. Exosomes from prostate and other cancer cells are increasingly proposed to play fundamental roles in modulating the tumor microenvironment and in metastasis. Here we review a diverse accessory gland literature, which highlights functional analogies between the male reproductive glands of flies and humans, and a critical role for extracellular vesicles in allowing seminal fluid to promote male interests within the female. We postulate that secondary cells and prostate epithelial cells use common mechanisms to control growth, secretion, and signaling, which are relevant to prostate and other cancers, and can be genetically dissected in the uniquely tractable fly model.
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Affiliation(s)
- C Wilson
- University of Oxford, Oxford, United Kingdom.
| | - A Leiblich
- University of Oxford, Oxford, United Kingdom; University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
| | | | - F Hamdy
- University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
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Angiotensin converting enzyme gene polymorphism studies: A case-control study. Saudi J Biol Sci 2015; 22:327-31. [PMID: 25972755 PMCID: PMC4423719 DOI: 10.1016/j.sjbs.2014.11.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Revised: 10/27/2014] [Accepted: 11/11/2014] [Indexed: 11/23/2022] Open
Abstract
Mild gestational hyperglycemia (MGH) is a very common complication of pregnancy that is characterized by intolerance to glucose. The association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism to MGH has been previously reported. In this study, we evaluated the association between ACE polymorphism and the risk of MGH in a Saudi population. We conducted a case-control study in a population of 100 MGH patients and 100 control subjects. ACE gene polymorphism was analyzed by the novel approach of tetraprimer amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR). The frequency of ACE polymorphism was not associated with either alleles or genotypes in MGH patients. Glucose concentration was found to be significantly associated with the MGH group. Our study suggests that ACE genotypes were not associated with ACE polymorphism in a Saudi population.
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Zhou X, Lin C. Survivin and angiotensin-converting enzyme polymorphisms with risk of colorectal cancer: a systematic review and meta-analysis. World J Surg Oncol 2015; 13:27. [PMID: 25889770 PMCID: PMC4347567 DOI: 10.1186/s12957-015-0461-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2014] [Accepted: 01/10/2015] [Indexed: 01/05/2023] Open
Abstract
Background Colorectal cancer (CRC) is the most common cause of cancer death worldwide. Numerous studies have identified the roles of survivin −31 G/C and angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms in CRC risk; however, the results remain inconclusive. This study was to investigate associations between these two polymorphisms and CRC susceptibility. Methods A comprehensive literature search was conducted to collect relevant case–control studies published between 2000 and 2014. The extracted data were statistically analyzed, and the odds ratios (ORs) with 95% confidence intervals (CIs) were employed to estimate the strength of association. Results A total of 11 studies were included in the meta-analysis. For survivin G/C polymorphism, six articles reported 1,840 cases and 1,804 controls. Overall, we found the frequency of C allele is higher in CRC cases than that in the healthy controls (57.2% vs. 48.0%), and C allele significantly increased the risk of CRC compared to G allele in allele model (OR = 1.46, 95% CI = 1.33–1.60, P < 0.00001). This association was also found in other genetic models (P < 0.00001). Stratified analysis by ethnicity showed significant association in each genetic model among the Asian population. For ACE I/D polymorphism, five studies included 758 cases and 6,755 controls. No significant association was found in any genetic models. Conclusions Our results showed that survivin −31 G/C polymorphism might contribute to risk of CRC, especially in the Asian populations. However, the ACE I/D polymorphism is not a genetic factor concerning the risk for CRC. More studies with larger sample sizes are required in the future.
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Affiliation(s)
- Xile Zhou
- Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, P.R. China.
| | - Caizhao Lin
- Department of Colorectal Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, P.R. China.
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