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The results from the published studies on the association between hypoxia-inducible factor-1(Hif-1/HIF-1) polymorphisms and cancer risk are conflicting. The common 1790G/A rs11549467) genetic polymorphism has been reported to be functional and may contribute to genetic susceptibility to cancers. However, the association between 1790G/A (rs11549467) and cancer risk remains inconclusive.To better understand the role of 1790G/A (rs11549467) polymorphism in cancer, we conducted this comprehensive meta-analysis encompassing 6337 cases and 9302 controls.Overall, the 1790G/A (rs11549467) genetic polymorphism was associated with higher cancer risk. In the stratified analysis, significant associations were found between the Hif-1/HIF-1 1790G/A polymorphism and lung cancer, pancreatic cancer and oral squamous cell carcinoma. We also observed that the AA genotype might modulate lung cancer (OR=5.42[2.75-10.70]), pancreatic cancer (OR=9.30[1.12-77.61]) and oral squamous cell carcinoma (OSCC) (OR=13.32[1.57-112.75]) risk comparing with the GG genotype. Moreover, a significantly increased cancer risk was found in homozygote comparison (AA vs. GG) and recessive genetic model (AA vs. AG/GG) among Caucasian population. When stratified by study design, significantly elevated susceptibility to cancer was found among hospital-based studies.These findings suggested that the 1790G/A (rs11549467) genetic polymorphism may contribute to the susceptibility of cancers except gynecologic cancer, especially in homozygote comparison and recessive genetic model among Caucasian population, and this SNP was significantly associated with the lung cancer, pancreatic cancer and oral squamous cell carcinoma (OSCC). The phenomenon also indicates that the SNP functions as a recessive mutation needs to be verified or linked with functional studies.

Update meta-analysis on 1790G/A polymorphism and cancer risk: Evidence from 26 studies