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Urol Oncol. 2017 Aug;35(8):532.e25-532.e30. doi: 10.1016/j.urolonc.2017.04.002. Epub 2017 May 2.

Hypoxia and renal cell carcinoma: The influence of HIF1A+1772C/T functional genetic polymorphism on prognosis.

Author information

1
Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, Porto, Portugal. Electronic address: martairferreira@sapo.pt.
2
Molecular Oncology and Viral Pathology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, Porto, Portugal.
3
Department of Medical Oncology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, Porto, Portugal.
4
Department of Urology, Portuguese Oncology Institute of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, Porto, Portugal.

Abstract

OBJECTIVES:

Hypoxia-inducible factor (HIF-1) is a key regulator of the genes involved in the cellular response to hypoxia. Overexpression of HIF-1 has been implicated in the pathogenesis of renal cell carcinoma (RCC), and functional polymorphisms of the HIF1A gene may confer susceptibility to RCC. Our purpose was to assess the influence of HIF1A+1772C/T (rs11549465) polymorphism on RCC prognosis.

MATERIAL AND METHODS:

This study evaluated the associations of the HIF1A+1772C/T (rs11549465) polymorphism with clinicopathologic prognostic factors, recurrence/progression, and survival in a cohort of 179 patients with RCC treated at Portuguese Oncology Institute of Porto. Genotyping analysis, using DNA extracted from peripheral blood, was performed by real-time polymerase chain reaction allelic discrimination. The genotype associations with clinicopathologic parameters and recurrence/progression were analyzed by the chi-square or Fisher tests. Genotypes influencing cancer-specific survival were compared using Cox proportional hazard regression, Kaplan-Meier curves, and Breslow test.

RESULTS:

None of the genotypes (CC, CT, or TT) were significantly associated with clinicopathologic prognostic factors. The TT genotype and T allele were associated with recurrence/progression (P = 0.042 and P = 0.02, respectively). Patients with CT and CT+TT genotypes tend to have an increased risk to RCC-related death (hazard ratio = 2.79; 95% CI: 0.88-8.82; P = 0.08 and hazard ratio = 2.76; 95% CI: 0.93-8.22; P = 0.07, respectively) and showed worse cancer-specific survival curves than those with the CC genotype (P = 0.012 and P = 0.018, respectively).

CONCLUSIONS:

These results suggest that HIF1A+1772C/T (rs11549465) polymorphism may have effects on RCC recurrence/progression and survival.

KEYWORDS:

Hypoxia-inducible factor; Prognosis; Renal cell carcinoma; Single nucleotide polymorphism

PMID:
28476527
DOI:
10.1016/j.urolonc.2017.04.002
[Indexed for MEDLINE]

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