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Hypoxia-Inducible Factor 1α Polymorphisms and Early-Stage Cervical Cancer
  1. Yun Hwan Kim, MD, PhD*,
  2. In-Ae Park, MD, PhD,
  3. Woong-Yang Park, MD, PhD,
  4. Jae Weon Kim, MD, PhD*,
  5. Seung Cheol Kim, MD, PhD§,
  6. Noh-Hyun Park, MD, PhD*,
  7. Yong-Sang Song, MD, PhD* and
  8. Soon-Beom Kang, MD, PhD*
  1. * Departments of Obstetrics and Gynecology,
  2. Pathology, and
  3. Biomedical Sciences, Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul; and
  4. § Department of Obstetrics and Gynecology, Medical Research Institute, School of Medicine, Ewha Woman's University, Seoul, Republic of Korea.
  1. Address correspondence and reprint requests to Soon-Beom Kang, MD, PhD, Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yongun-Dong, Chongno-Gu, Seoul 110-744, Republic of Korea. E-mail: ksboo308{at}gmail.com; medok74{at}gmail.com.

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.

  • HIF-1α
  • Polymorphism
  • Lymph node metastasis
  • Survival
  • Cervical cancer

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