The association between the rs11549465 polymorphism in the hif-1α gene and cancer risk: a meta-analysis.

PURPOSE:The associations between hypoxia-inducible factor-1 alpha (HIF-1alpha) and clinicopathological characteristics of cancers have been evaluated in various studies, with the conflicting results. The common rs11549465 (1772C/T) genetic polymorphism has been reported to be functional and may contribute to genetic susceptibility to cancers. However, the association between rs11549465 (1772C/T) and cancer risk remains inconclusive. METHODS:To better understand the role of rs11549465 (1772C/T) polymorphism in global cancer, we conducted this comprehensive meta-analysis encompassing 7807 cases and 8633 controls. RESULTS:Overall, the rs11549465 (1772C/T) genetic polymorphism was associated with higher cancer risk, especially exists in Asians. In the stratified analysis, significant associations were found between the HIF-1 rs11549465 polymorphism and gynecologic cancer among Caucasian population. We observed that the TT genotype might modulate gynecologic cancer (OR=9.92 [2.15-45.66]) risk comparing with the CC genotype. Moreover, a significantly increased lung and breast cancer risk was found among Asian population comparing with Caucasian population. When stratified by study design, significantly elevated susceptibility to cancer was found among hospital -based studies. CONCLUSIONS:Our meta-analysis suggested that the HIF-1 rs11549465 (1772C/T) genetic polymorphism is significantly associated with higher risk among Asian population and lower risk among Caucasian population in breast and lung cancer, and this SNP was significantly associated with the gynecologic cancer among Caucasian population. The effect of the rs11549465 polymorphism on cancer especially exists in Asians.