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

Fraga, Avelino; Ribeiro, Ricardo; Príncipe, Paulo; Lobato, Carlos; Pina, Francisco; Maurício, Joaquina; Monteiro, Cátia; Sousa, Hugo; Silva, F. Calais da; Lopes, Carlos; Medeiros, Rui

doi:10.1016/j.ejca.2013.09.001

Cited by 25 publications

(19 citation statements)

References 36 publications

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“…Among the remaining reports, 24 more were removed for basic research ( n = 6), not involving HIF1A rs11549465 polymorphism ( n = 13), and no controls ( n = 5). As a consequence, a total of 4,570 cases and 4,820 controls were included in the present study [ 14 , 24 – 29 ]. Table 1 describes principal characteristics of these included studies.…”

Section: Resultsmentioning

confidence: 99%

“…Besides, a replicated association was revealed as well among Jewish people in a research by Orr-Urtreger et al [ 28 ]. Nevertheless, Fraga et al suggested that HIF1A rs11549465 polymorphism was not related to the risk of prostate cancer [ 29 ]. In addition, Jacobs et al and Li et al also insisted that the SNP had no significant impact on susceptibility to prostate cancer in their studies [ 14 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

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Association betweenHIF1Ars11549465 polymorphism and risk of prostate cancer: a meta-analysis

Fang

et al. 2017

Oncotarget

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The hypoxia inducible factor 1-alpha (HIF1A) gene has been suggested to play a critical role in cancer progression, and the relationship between HIF1A rs11549465 polymorphism and risk of prostate cancer has been investigated in previous studies. Nevertheless, conflicting results have been obtained. Hence, we reevaluated this issue by means of this meta-analysis, with the purpose of providing more precise conclusion on this issue. The electronic databases of PubMed, EMBASE and Chinese National Knowledge Infrastructure (CNKI) as well as other sources were searched for relevant reports concerning on the role of HIF1A rs11549465 polymorphism in the occurrence of prostate cancer. The strength of the relationship was determined by calculating odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs). Besides, subgroup analyses by ethnicity and source of control were further performed to examine this relationship. All statistical analyses were performed using STATA software 12.0. Although HIF1A rs11549465 polymorphism showed a tendency of increasing the risk of prostate cancer, no statistical significance was detected under any genetic models. Similar results were also revealed in subgroup analyses on the basis of ethnicity and control source. Our findings indicate that HIF1A rs11549465 polymorphism may not independently play a significant role in the occurrence of prostate cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association betweenHIF1Ars11549465 polymorphism and risk of prostate cancer: a meta-analysis

Fang

et al. 2017

Oncotarget

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“…Therefore, hypoxia in the tumor microenvironment may be a crucial factor for promoting the progression of several types of cancer, including gastric tumors (3). Hypoxia-inducible factor-1α (HIF1A) is a regulatory factor critical for the adaptation of tumor cells to a hypoxic environment (4,5), and its overexpression can promote tumor growth and metastasis through inducing tumor angiogenesis (6,7). The expression of HIF1A appears to be potentiated in numerous types of human cancer, including colorectal (8) and edometrioid carcinomas (9), breast (10), pancreatic (11), prostate (12) and ovarian cancer (13), and many more (14,15).…”

Section: Introductionmentioning

confidence: 99%

PHD3 affects gastric cancer progression by negatively regulating HIF1A

Xia

Jiang

et al. 2017

Molecular Medicine Reports

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Prolyl hydroxylase 3 (PHD3) is widely accepted as a tumor suppressor; however, the expression of PHD3 in various cancer types remains controversial. The present study aimed to investigate the association between PHD3 expression and the clinicopathological features of gastric cancer using reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry. The effects of PHD3 in gastric cancer cell lines were assessed using western blot analysis and transwell migration assays. The present results revealed that PHD3 expression was increased in adjacent non‑cancerous tissue compared with in gastric cancer tissue, and PHD3 overexpression was correlated with the presence of well‑differentiated cancer cells, early cancer stage classification and the absence of lymph node metastasis. In vitro experiments demonstrated that PHD3 may act as a negative regulator of hypoxia‑inducible factor‑1α and vascular endothelial growth factor, both of which participate in tumor angiogenesis. In conclusion, the present results suggested that PHD3 may act as a tumor suppressor in gastric cancer. Therefore, the targeted regulation of PHD3 may have potential as a novel therapeutic approach for the treatment of patients with gastric cancer.

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“…Recently, functionally active genetic variants in the HIF-1α (C/T; Single Nucleotide Polymorphism (SNP) rs11549465) and the PHD2 gene ( EGLN1 ; C/T; SNP rs516651 and T/C; SNP rs480902) were identified [ 3 – 5 ] and were associated with increased HIF-1α nuclear translocation and a worse outcome compared to the TT-genotype in several tumors [ 6 ]. However, the HIF-1-pathway plays an important role in adaptation to inflammation, too, as both HIF-1α mRNA and intracellular HIF-1α protein are highly increased following inflammatory stimuli [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia inducible factor-1 alpha and prolinhydroxlase 2 polymorphisms in patients with severe sepsis: a prospective observational trial

et al. 2015

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BackgroundHypoxia-inducible-factor-1α (HIF-1α) and HIF-1 degrading prolyl-hydroxylases (PHD) are key regulators of the hypoxic-inflammatory response. Functionally active genetic variants in the HIF-1α (C/T; Single Nucleotide Polymorphism (SNP) rs11549465) and the PHD2 gene (EGLN1; C/T; SNP rs516651 and T/C; SNP rs480902) are associated with altered HIF-1α mRNA nuclear translocation and an altered adaptation to hypoxia. Furthermore, the HIF system is important in surviving inflammatory disorders and sepsis. Thus, we tested the hypotheses, that SNPs in the HIF-1α or PHD2 genes are (1) common in Caucasians, with 2) the HIF-1α genetic variant being associated with an altered HIF-1α mRNA expression; and 3) independent risk factors for 30-day mortality in severe sepsis.MethodsAfter ethics approval, 128 septic patients (Caucasian descent) were included prospectively within 24 h after first diagnosing sepsis. Patients characteristics and severity of illness (simplified acute physiology score II), genotypes (Taqman assay), and their influence on leukocyte HIF-1α-mRNA-expression (Real-Time PCR) and 30-day mortality were determined.ResultsFrequencies were 0.8 % for homozygous HIF-1α TT-carriers (CT 17.6 %; CC 81.6 %), 2.5 % for homozygous PHD2 SNP rs516651 TT-allele carriers (CT 17.5 % and CC 80 %), and 9.4 % for homozygous PHD2 SNP rs480902 TT-allele carriers (CT 34.4 % and CC 56.3 %). While HIF-1α T-allele carriers had a borderline decrease in HIF-1α-mRNA-expression (p = 0.06) neither HIF-1α nor PHD2 SNPs were (independent) risk factors for 30-day mortality.ConclusionsGenetic variants in HIF-1α and PHD2 genes exist in Caucasians but do not appear to alter 30-day mortality in sepsis.

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

Cited by 25 publications

References 36 publications

Association betweenHIF1Ars11549465 polymorphism and risk of prostate cancer: a meta-analysis

Association betweenHIF1Ars11549465 polymorphism and risk of prostate cancer: a meta-analysis

PHD3 affects gastric cancer progression by negatively regulating HIF1A

Hypoxia inducible factor-1 alpha and prolinhydroxlase 2 polymorphisms in patients with severe sepsis: a prospective observational trial

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