The association between hypoxia-inducible factor-1 α gene G1790A polymorphism and cancer risk: a meta-analysis of 28 case–control studies

PURPOSE: Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates the cellular adaptation to hypoxia. HIF-1α gene single nucleotide polymorphisms (SNPs) are implicated to be associated with cancer risks. However, results from the published studies remained inconclusive. The aim of this study is to investigate the relationship of HIF-1α gene G1790A polymorphism with cancer using meta-analysis. METHODS: A comprehensive search in Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) was conducted to identify all publications on the association between this polymorphism and cancer until December 13, 2013. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to evaluate the strength of this association. Association between lymph node metastasis and G1790A was also investigated. RESULTS: A total of 5985 cases and 6809 controls in 28 case–control studies were included in this meta-analysis. The A allele of HIF-1α gene G1790A polymorphism was found to be significantly associated with increased cancer risk in four genetic models: AA + AG vs. GG (dominant model OR = 1.85, 95% CI = 1.27-2.69), AA vs. AG + GG (recessive model OR = 5.69, 95% CI = 3.87-8.37), AA vs. GG (homozygote comparison OR = 6.63, 95% CI = 4.49-9.79), and AG vs. GG (heterozygote comparison OR = 2.39, 95% CI = 1.53-3.75). This variant was also significantly associated with higher risks of pancreatic cancer, head and neck cancer, lung cancer and renal cell carcinoma. However, the A allele of G1790A was not significantly associated with increased lymph node metastasis in the dominant model by overall meta-analysis. CONCLUSIONS: Our meta-analysis suggests that the substitution of G with A of HIF-1α gene G1790A polymorphism is a risk factor of cancer, especially for pancreatic cancer, lung cancer, renal cell carcinoma and head and neck cancer. The association is significant in Asian, Caucasian population and public based control subgroups. However, it’s not associated with risk of lymph node metastasis.