BackgroundHypoxia inducible factor 1-alpha (HIF1A) is a transcription factor that plays important role in regulating cascade of reactions. In this study, the effect of rs11549465 (1772 C/T) and rs11549467 (1790 G/A) polymorphisms of HIF1A gene and its association with cancers were investigated through meta-analysis.MethodsMeta-analysis of genome wide association studies of HIF1A 1772 C/T polymorphism were conducted on 22 case-control studies of sample size 19024 and for 1790 G/A polymorphism 19 case-control studies were included with sample size 10654. Genotype and allelic frequency compared between cases and controls together with further subgroup analyses were carried out by cancer type and ethnicity.ResultsMeta-analysis from this study indicated that HIF1A 1772 C/T polymorphism is significantly associated with overall cancer risk. T allele and genotype TT are significantly associated with increasing overall cancer risk; odds ratios (OR) dominant model [TT + CT vs. CC: OR 1.30, 95 % CI (1.06-1.59), p-value: 0.0115], and T allele vs. C allele: OR 1.32, 95 % CI (1.07-1.63), p-value: 0.0098. Also, HIF1A 1790 G/A polymorphism, analyses showed that A allele and genotype AA are significantly associated with increasing overall cancer risk; odds ratios (OR) homozygote comparison [AA vs. GG: OR 5.10, 95 % CI (3.12-8.33), p-value: <0.0001], heterozygote comparison [GA vs. GG: OR 1.74, 95 % CI (1.20-2.52), p-value: 0.0033], dominant model [AA + GA vs. GG: OR 1.82, 95 % CI (1.26-2.62), p-value: 0.0014], recessive model [AA vs. GA + GG: OR 3.79, 95 % CI (2.34-6.15), p-value: <0.0001] and A allele vs. G allele: OR 1.82, 95 % CI (1.31-2.52), p-value: 0.0003.ConclusionIn detail meta-analysis indicated that both the polymorphisms 1772 C/T and 1790 G/A are significantly associated with overall cancer risk. The subgroup analyses showed that lung cancer is significantly associated with both polymorphisms. Although the 1772 C/T polymorphism is significantly associated with decreasing risk of renal cell carcinoma but the 1790 G/A polymorphism has shown to significantly increase the cancer risk in both Caucasian and Asian population. Thus, HIF1A could be a useful prognostic marker for cancers early predisposition.Electronic supplementary materialThe online version of this article (doi:10.1186/s40364-015-0054-z) contains supplementary material, which is available to authorized users.

Athletic performance is a polygenic trait influenced by both environmental and genetic factors.1 Genetics has a great influence over athletic performance such as strength, power, muscle fibre, flexibility and other phenotypes. HIF1A (hypoxia inducible factor 1 alpha), a master-regulator of oxygen-homeostasis, plays crucial roles in cellular metabolism.2 HIF1A regulates expression of nearly all enzymes involved in glycolysis. HIF1A mediates oxygen delivery to cells as well as allows cells to survive under oxygen deprivation by regulating expression of hundreds of genes involved in angiogenesis, erythropoiesis glucose metabolism and transport.2,3 The HIF1A gene is considered as a genetic marker of athletic ability because of its proposed role in shifting of oxidative type muscle fibres to glycolytic type and increasing hypoxia resistance to the cells.4 The aim of this study was to perform a meta-analysis of all available case-control-studies of athletes to systematically summarise the association between HIF1A C1772T (rs11549465) polymorphism and athletic performance.Literature-mining was performed for the last 15 years using PubMed and Google Scholar to retrieve relevant case-control studies. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated using fixed or random effects model incorporating inverse-variance-weighted method for relating HIF1A 1772 C/T polymorphism (rs11549465; which results in Pro582Ser substitutions) with elite athlete’s performance. In subgroup analyses top-level athletes were considered as ‘elite athletes’ who were competing in the Olympics Games &/World and European championships and won medals; and ‘other athletes’ being national level and regional competitors with no less than four years of experience participating in their sport. The distributions of genotypes in the controls were checked for HWE. Further subgroup-analysis of HIF1A 1772 C/T was carried out by ethnicity.A meta-analysis of 19 studies comprising 1616 cases and 9253 controls was conducted to identify the association of HIF1A rs11549465 (C/T) polymorphism with elite athlete’s performance. Results demonstrated that the T allele is significantly associated with elite athletes under three genetic models (TT+CT vs CC: OR = 1.73, 95% CI: = 1.22–2.46, p 0.002); (CT vs CC: OR = 1.73, 95% CI: = 1.21–2.47, p 0.003); (T vs C: OR = 1.64, 95% CI: = 1.19–2.25, p 0.002) whereas other athletes group showed no significant associations (TT+CT vs CC: OR = 1.44, 95% CI: = 0.72–2.88, p 0.30); (CT vs CC: OR = 1.37, 95% CI: = 0.65–2.89, p 0.40); (T vs C: OR = 1.38, 95% CI: = 0.84–2.29, p 0.20). For elite athletes no significant heterogeneity was observed (T vs C: I^2 = 60.8% [0% - 86.9%]; Q = 7.6; p 0.054). For Caucasian population, sub-group analyses data suggested that the HIF1A 1772 C/T polymorphism is highly associated with athletic performance in three models (TT+CT vs CC: OR = 1.51, 95% CI: = 1.15–1.98, p 0.003); (CT vs CC: OR = 1.53, 95% CI: = 1.17–2.01, p 0.002); (T vs C: OR = 1.41, 95% CI: = 1.1–1.80, p 0.005).Results from th...