دورية أكاديمية
The HIF1A Functional Genetic Polymorphism at Locus +1772 Associates with Progression to Metastatic Prostate Cancer and Refractoriness to Hormonal Castration
| العنوان: | The HIF1A Functional Genetic Polymorphism at Locus +1772 Associates with Progression to Metastatic Prostate Cancer and Refractoriness to Hormonal Castration |
|---|---|
| المؤلفون: | Fraga, A, Ribeiro, R, Príncipe, P, Lobato, C, Pina, F, Maurício, J, Monteiro, C, Sousa, H, Calais da Silva, F, Lopes, C, Medeiros, R |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2014 |
| المجموعة: | Repositório do Centro Hospitalar de Lisboa Central EPE |
| مصطلحات موضوعية: | CHLC URO, Alelos, Antagonistas de Androgénios, Progressão da Doença, Resistência a Medicamentos Antineoplásicos, Razão de Possibilidades, Metástase de Neoplasia, Polimorfismo de Nucleotídeo Único, Prognóstico, Neoplasias da Próstata, Frequência do Gene, Genótipo, Subunidade Alfa do Factor 1 Induzível por Hipóxia, Modelos Logísticos, Análise Multivariada |
| الوصف: | The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | Eur J Cancer. 2014 Jan;50(2):359-65.; http://hdl.handle.net/10400.17/1860Test |
| الإتاحة: | http://hdl.handle.net/10400.17/1860Test |
| حقوق: | openAccess |
| رقم الانضمام: | edsbas.B8486152 |
| قاعدة البيانات: | BASE |
| ResultId |
1 |
|---|---|
| Header |
edsbas BASE edsbas.B8486152 855 3 Academic Journal academicJournal 854.518249511719 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsbas&AN=edsbas.B8486152&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => http://hdl.handle.net/10400.17/1860# [Name] => EDS - BASE [Category] => fullText [Text] => View record in BASE [MouseOverText] => View record in BASE ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => The HIF1A Functional Genetic Polymorphism at Locus +1772 Associates with Progression to Metastatic Prostate Cancer and Refractoriness to Hormonal Castration
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Fraga%2C+A%22">Fraga, A</searchLink><br /><searchLink fieldCode="AR" term="%22Ribeiro%2C+R%22">Ribeiro, R</searchLink><br /><searchLink fieldCode="AR" term="%22Príncipe%2C+P%22">Príncipe, P</searchLink><br /><searchLink fieldCode="AR" term="%22Lobato%2C+C%22">Lobato, C</searchLink><br /><searchLink fieldCode="AR" term="%22Pina%2C+F%22">Pina, F</searchLink><br /><searchLink fieldCode="AR" term="%22Maurício%2C+J%22">Maurício, J</searchLink><br /><searchLink fieldCode="AR" term="%22Monteiro%2C+C%22">Monteiro, C</searchLink><br /><searchLink fieldCode="AR" term="%22Sousa%2C+H%22">Sousa, H</searchLink><br /><searchLink fieldCode="AR" term="%22Calais+da+Silva%2C+F%22">Calais da Silva, F</searchLink><br /><searchLink fieldCode="AR" term="%22Lopes%2C+C%22">Lopes, C</searchLink><br /><searchLink fieldCode="AR" term="%22Medeiros%2C+R%22">Medeiros, R</searchLink> ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Elsevier ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2014 ) Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => Repositório do Centro Hospitalar de Lisboa Central EPE ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22CHLC+URO%22">CHLC URO</searchLink><br /><searchLink fieldCode="DE" term="%22Alelos%22">Alelos</searchLink><br /><searchLink fieldCode="DE" term="%22Antagonistas+de+Androgénios%22">Antagonistas de Androgénios</searchLink><br /><searchLink fieldCode="DE" term="%22Progressão+da+Doença%22">Progressão da Doença</searchLink><br /><searchLink fieldCode="DE" term="%22Resistência+a+Medicamentos+Antineoplásicos%22">Resistência a Medicamentos Antineoplásicos</searchLink><br /><searchLink fieldCode="DE" term="%22Razão+de+Possibilidades%22">Razão de Possibilidades</searchLink><br /><searchLink fieldCode="DE" term="%22Metástase+de+Neoplasia%22">Metástase de Neoplasia</searchLink><br /><searchLink fieldCode="DE" term="%22Polimorfismo+de+Nucleotídeo+Único%22">Polimorfismo de Nucleotídeo Único</searchLink><br /><searchLink fieldCode="DE" term="%22Prognóstico%22">Prognóstico</searchLink><br /><searchLink fieldCode="DE" term="%22Neoplasias+da+Próstata%22">Neoplasias da Próstata</searchLink><br /><searchLink fieldCode="DE" term="%22Frequência+do+Gene%22">Frequência do Gene</searchLink><br /><searchLink fieldCode="DE" term="%22Genótipo%22">Genótipo</searchLink><br /><searchLink fieldCode="DE" term="%22Subunidade+Alfa+do+Factor+1+Induzível+por+Hipóxia%22">Subunidade Alfa do Factor 1 Induzível por Hipóxia</searchLink><br /><searchLink fieldCode="DE" term="%22Modelos+Logísticos%22">Modelos Logísticos</searchLink><br /><searchLink fieldCode="DE" term="%22Análise+Multivariada%22">Análise Multivariada</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT. ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article in journal/newspaper ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => NoteTitleSource [Label] => Relation [Group] => SrcInfo [Data] => Eur J Cancer. 2014 Jan;50(2):359-65.; http://hdl.handle.net/10400.17/1860 ) Array ( [Name] => URL [Label] => Availability [Group] => URL [Data] => http://hdl.handle.net/10400.17/1860 ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => openAccess ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsbas.B8486152 ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => CHLC URO
[Type] => general
)
[1] => Array
(
[SubjectFull] => Alelos
[Type] => general
)
[2] => Array
(
[SubjectFull] => Antagonistas de Androgénios
[Type] => general
)
[3] => Array
(
[SubjectFull] => Progressão da Doença
[Type] => general
)
[4] => Array
(
[SubjectFull] => Resistência a Medicamentos Antineoplásicos
[Type] => general
)
[5] => Array
(
[SubjectFull] => Razão de Possibilidades
[Type] => general
)
[6] => Array
(
[SubjectFull] => Metástase de Neoplasia
[Type] => general
)
[7] => Array
(
[SubjectFull] => Polimorfismo de Nucleotídeo Único
[Type] => general
)
[8] => Array
(
[SubjectFull] => Prognóstico
[Type] => general
)
[9] => Array
(
[SubjectFull] => Neoplasias da Próstata
[Type] => general
)
[10] => Array
(
[SubjectFull] => Frequência do Gene
[Type] => general
)
[11] => Array
(
[SubjectFull] => Genótipo
[Type] => general
)
[12] => Array
(
[SubjectFull] => Subunidade Alfa do Factor 1 Induzível por Hipóxia
[Type] => general
)
[13] => Array
(
[SubjectFull] => Modelos Logísticos
[Type] => general
)
[14] => Array
(
[SubjectFull] => Análise Multivariada
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => The HIF1A Functional Genetic Polymorphism at Locus +1772 Associates with Progression to Metastatic Prostate Cancer and Refractoriness to Hormonal Castration
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Fraga, A
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Ribeiro, R
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Príncipe, P
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Lobato, C
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Pina, F
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Maurício, J
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Monteiro, C
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Sousa, H
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Calais da Silva, F
)
)
)
[9] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Lopes, C
)
)
)
[10] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Medeiros, R
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 01
[Type] => published
[Y] => 2014
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-locals
[Value] => edsbas
)
[1] => Array
(
[Type] => issn-locals
[Value] => edsbas.oa
)
)
)
)
)
)
)
|
| IllustrationInfo |