Association of <i>Hypoxia-Inducible Factor 1α</i> Gene Polymorphisms With Breast Cancer Susceptibility: A Meta-Analysis.

Abstract

Overexpression of the <i>hypoxia-inducible factor 1α (HIF1A)</i> gene is significantly associated with different types of cancers, including breast cancer. In this study, the effects of single-nucleotide polymorphisms rs11549465, rs11549467, and rs2057482 of the <i>HIF1A</i> gene and their association with breast cancer were systematically investigated through meta-analysis. After a systematic review, nine case-control studies of the <i>HIF1A</i> rs11549465 C/T polymorphism, six case-control studies of the <i>HIF1A</i> rs11549467 G/A polymorphism, and one case-control study of the <i>HIF1A</i> rs2057482 C/T polymorphism were included in this meta-analysis. The summary pooled odds ratios with 95% CIs were evaluated to detect the relationship between <i>HIF1A</i> polymorphisms and breast cancer susceptibility. Subgroup-stratified analyses showed that the T and TT genotypes of the <i>HIF1A</i> rs11549465 C/T polymorphism were significantly associated with increased breast cancer risk in the Asian population under three genetic models (allele, homozygous, and recessive). <i>HIF1A</i> rs11549467 G/A analyses indicated that the A and AA genotypes were significantly associated with increased breast cancer risk in the Asian population under allele and dominant models. However, no association with breast cancer was observed in the White population for the <i>HIF1A</i> rs11549465 C/T and rs11549467 G/A polymorphisms. In addition, the <i>HIF1A</i> rs2057482 C/T polymorphism showed no association with breast cancer under any genetic models or by ethnicity-stratified analyses. The results of this meta-analysis suggested that the <i>HIF1A</i> rs11549465 C/T and rs1154946 G/A polymorphisms were significantly associated with increased breast cancer risk in the Asian population, but no associations were found in the White population. Thus, <i>HIF1A</i> could be an important biomarker for population-based breast cancer screening.