Association of Hypoxia-Inducible Factor 1α Gene Polymorphisms With Breast Cancer Susceptibility: A Meta-Analysis

Abstract

PURPOSE Overexpression of the hypoxia-inducible factor 1α (HIF1A) 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 HIF1A gene and their association with breast cancer were systematically investigated through meta-analysis. MATERIALS AND METHODS After a systematic review, nine case-control studies of the HIF1A rs11549465 C/T polymorphism, six case-control studies of the HIF1A rs11549467 G/A polymorphism, and one case-control study of the HIF1A 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 HIF1A polymorphisms and breast cancer susceptibility. RESULTS Subgroup-stratified analyses showed that the T and TT genotypes of the HIF1A rs11549465 C/T polymorphism were significantly associated with increased breast cancer risk in the Asian population under three genetic models (allele, homozygous, and recessive). HIF1A 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 HIF1A rs11549465 C/T and rs11549467 G/A polymorphisms. In addition, the HIF1A rs2057482 C/T polymorphism showed no association with breast cancer under any genetic models or by ethnicity-stratified analyses. CONCLUSION The results of this meta-analysis suggested that the HIF1A 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, HIF1A could be an important biomarker for population-based breast cancer screening.