Hypoxia-inducible factor 1α polymorphisms and early-stage cervical cancer

Int J Gynecol Cancer. 2011 Jan;21(1):2-7. doi: 10.1097/IGC.0b013e318204f6e6.

Abstract

Background: Human papillomavirus can stabilize and induce hypoxia-inducible factor 1α (HIF-1α) protein, which is associated with diminished response to treatment and poor prognosis for cervical cancer. Hypoxia-inducible factor 1α polymorphisms (1772C>T and 1790G>A) in the N-terminal transactivation domain generate significantly increased transcriptional activity and have been linked to poor outcome in various malignancies.

Objective: The aim of this study was to analyze the possible influence of HIF-1α genetic polymorphisms on cancer susceptibility, tumor aggressiveness, and survival of patients with early-stage cervical cancer.

Methods: One hundred ninety-nine patients with early-stage cervical cancer who were treated with surgical resection were retrospectively investigated. Hypoxia-inducible factor 1α 1772C>T and 1790G>A genetic polymorphisms were compared with 205 healthy subjects and correlated with the clinical outcome of patients with early-stage cervical cancer.

Results: The risk of cervical cancer was not affected by HIF-1α 1772C>T and 1790G>A polymorphisms. However, lymph node metastasis was significantly increased in patients who had the 1790 variant (adjusted odds ratio, 5.01; 95% confidence interval, 1.05-23.88; P = 0.043). In survival analysis, HIF-1α 1772C>T and 1790G>A polymorphisms were not related to disease-free survival and overall survival.

Conclusions: Although HIF-1α genetic polymorphisms had little association with cervical cancer risk and prognosis, individual variance of HIF-1α gene may be associated with cervical cancer invasiveness.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Alleles
  • Carcinoma, Small Cell / genetics*
  • Carcinoma, Small Cell / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Middle Aged
  • Mixed Function Oxygenases
  • Polymorphism, Genetic*
  • Repressor Proteins / genetics*
  • Retrospective Studies
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Repressor Proteins
  • Mixed Function Oxygenases
  • HIF1AN protein, human