The association between hypoxia-inducible factor-1 α gene C1772T polymorphism and cancer risk: a meta-analysis of 37 case-control studies

PLoS One. 2013 Dec 18;8(12):e83441. doi: 10.1371/journal.pone.0083441. eCollection 2013.

Abstract

Background: The possible association between HIF-1α C1772T polymorphism and cancer risk has been studied extensively. However, the results were controversial. In order to get a more precise conclusion of this association, a meta-analysis was performed.

Methods: A total of 10186 cases and 10926 controls in 37 case-control studies were included in this meta-analysis. Allele and genotypic differences between cases and controls were evaluated. Subgroup analysis by cancer site, ethnicity, source of controls and gender was performed.

Results: The T allele of HIF-1α gene C1772T was significantly associated with increased cancer risk in three genetic models: TT+CT vs.CC (dominant model OR=1.23, 95%CI=1.03-1.47), TT vs. CT+CC (recessive model OR=2.51, 95%CI=1.54-4.09), TT vs. CC (homozygote comparison OR=2.02, 95%CI=1.21-3.39).In subgroup analysis, the frequency of the T variant was found to be significantly increased in cervical cancer, pancreatic cancer, head and neck cancer, renal cell carcinoma, Asian and female subgroups.

Conclusions: Our meta-analysis suggests that the substitution of C allele with T at HIF-1α gene C1772T polymorphism is a risk factor of cancer, especially for cervical, head and neck cancer, pancreatic cancer and renal cell carcinoma. It is also a risk factor of cancer in Asian group as well as in female group.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Neoplasms / genetics*
  • Polymorphism, Genetic*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81061120531, 81200791, 30930100, 81102060, and 81001208), the International Science and Technology Cooperation Program of China (No. 2012DFA31370), and Doctoral Program of the Ministry of Education of China (No. 20110181110055, 20100181120057). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.