The HIF1A functional genetic polymorphism at locus+1772 associates with progression to metastatic prostate cancer and refractoriness to hormonal castration

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Fraga, A (Author) Other; Ribeiro, R (Author) Other; Principe, P (Author) Other; Lobato, C (Author) Other; Pina, F (Author) Other; Mauricio, J (Author) Other; Monteiro, C (Author) Other; Sousa, H (Author) Other; da Silva, FC (Author) Other; Lopes, C (Author) Other; Rui Medeiros (Author) ICBAS

Journal

Title: European Journal of Cancer

Vol. 50

Pages: 359-365

ISSN: 0959-8049

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 23 Citations

Scopus - 23 Citations

Other information

Authenticus ID: P-009-34M

DOI: 10.1016/j.ejca.2013.09.001

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7