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

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, 1.05Y23.88; 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. Copyright © 2010 by IGCS and ESGO.