The Association between Hypoxia-Inducible Factor-1 α Gene C1772T Polymorphism and Cancer Risk: A Meta-Analysis of 37 Case-Control Studies

Abstract

BackgroundThe possible association between HIF-1α C1772T polymorphism and cancer risk has been studied extensively. However, the results were controversial. In order to get a more precise conclusion of this association, a meta-analysis was performed. MethodsA total of 10186 cases and 10926 controls in 37 case-control studies were included in this meta-analysis. Allele and genotypic differences between cases and controls were evaluated. Subgroup analysis by cancer site, ethnicity, source of controls and gender was performed.ResultsThe T allele of HIF-1α gene C1772T was significantly associated with increased cancer risk in three genetic models: TT+CT vs.CC (dominant model OR=1.23, 95%CI=1.03-1.47), TT vs. CT+CC (recessive model OR=2.51, 95%CI=1.54-4.09), TT vs. CC (homozygote comparison OR=2.02, 95%CI=1.21-3.39).In subgroup analysis, the frequency of the T variant was found to be significantly increased in cervical cancer, pancreatic cancer, head and neck cancer, renal cell carcinoma, Asian and female subgroups.ConclusionsOur meta-analysis suggests that the substitution of C allele with T at HIF-1α gene C1772T polymorphism is a risk factor of cancer, especially for cervical, head and neck cancer, pancreatic cancer and renal cell carcinoma. It is also a risk factor of cancer in Asian group as well as in female group.

No Association of Hypoxia Inducible Factor-1α Gene Polymorphisms with Breast Cancer in North-West Indians

“…Meta-analysis has revealed HIF-1α g.C1772T polymorphism as a risk factor of cancer in females in Asian population (He et al, 2013) and it can also increase the risk of cancer metastasis . In recent meta-analysis, T allele of g.C1772T polymorphism has been significantly associated with increased risk of cancer in Asians rather than Caucasians (Wu et al, 2014).…”

Association between Hypoxia-inducible Factor-1α gene polymorphisms and risk of chronic hepatitis b and hepatitis b virus-related liver cirrhosis in a Chinese population: A retrospective case–control study

“…(Semenza, 2000). Thus far, the pathophysiology of human disease in which HIF-1 is involved includes myocardial ischemia, cerebral ischemia, retinal ischemia, pulmonary hypertension, preeclampsia, intrauterine growth retardation (Semenza, 2000), as well as various cancers (He et al, 2013;Xu et al, 2013;Ye et al, 2014). Recently, a constantly growing body of evidence also suggests that HIF-1 plays a novel and important role in inflammatory diseases and immune responses (Cramer et al, 2003), including antibacterial and antiviral innate immune responses (Zinkernagel et al, 2007).…”

The Association between the C1772T Genetic Polymorphism in Human HIF-1α Gene and Breast Cancer Risk: A Meta-analysis

“…The C1772T is detected within the oxygen-dependent degradation (ODD)/pVHL binding domain in exon 12 of the HIF-1α gene [13]. The C1772T, especially genotypes with T allele (TT or CT) [18] is showed than it can strengthen a significant transcriptional activity of the HIF-1α [13]. There are reasons for the effect of The C1772T on HIF-1α.…”