Dataset Information

Hypoxia-inducible factor-1alpha gene polymorphisms and cancer risk: a meta-analysis.

ABSTRACT:

Background

The results from the published studies on the association between hypoxia-inducible factor -1alpha (HIF-1alpha) polymorphisms and cancer risk are conflicting. In this meta-analysis, we aimed to investigate the association between HIF-1alpha 1772 C/T and 1790 G/A polymorphisms and cancer.

Methods

The meta-analysis for 1772 C/T polymorphism included 4131 cancer cases and 5387 controls, and for 1790 G/A polymorphism included 2058 cancer cases and 3026 controls. Allelic and genotypic comparisons between cases and controls were evaluated. Subgroup analyses by cancer types, ethnicity, and gender were also performed. We included prostate cancer in male subgroup, and female specific cancers in female subgroup.

Results

For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with higher cancer risk: odds ratio (OR) = 1.29 [95% confidence interval (CI, 1.01, 1.65)], P = 0.04, P(heterogeneity) < 0.00001, and OR = 2.18 [95% CI (1.32, 3.62)], P = 0.003, P(heterogeneity) = 0.02, respectively. The effect of the genotype TT on cancer especially exists in Caucasians and female subjects: OR = 2.40 [95% CI (1.26, 4.59)], P = 0.008, P(heterogeneity) = 0.02, and OR = 3.60 [95% CI (1.17, 11.11)], P = 0.03, P(heterogeneity) = 0.02, respectively. For the 1790 G/A polymorphism, the pooled ORs for allelic frequency comparison and dominant model comparison suggested a significant association of 1790 G/A polymorphism with a decreased breast cancer risk: OR = 0.28 [95% CI (0.08, 0.90)], P = 0.03, P(heterogeneity) = 0.45, and OR = 0.29 [95% CI (0.09, 0.97)], P = 0.04, P(heterogeneity) = 0.41, respectively. The frequency of the HIF-1alpha 1790 A allele was very low and only two studies were included in the breast cancer subgroup.

Conclusions

Our meta-analysis suggests that the HIF-1alpha 1772 C/T polymorphism is significantly associated with higher cancer risk, and 1790 G/A polymorphism is significantly associated with decreased breast cancer risk. The effect of the 1772 C/T polymorphism on cancer especially exists in Caucasians and female subjects. Only female specific cancers were included in female subgroup, which indicates that the 1772 C/T polymorphism is significantly associated with an increased risk for female specific cancers. The association between the 1790 G/A polymorphism and lower breast cancer risk could be due to chance.

SUBMITTER: Zhao T

PROVIDER: S-EPMC2804603 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hypoxia-inducible factor-1alpha gene polymorphisms and cancer risk: a meta-analysis.

Zhao Tongfeng T Lv Jing J Zhao Jiangpei J Nzekebaloudou Marius M

Journal of experimental & clinical cancer research : CR 20091227

<h4>Background</h4>The results from the published studies on the association between hypoxia-inducible factor -1alpha (HIF-1alpha) polymorphisms and cancer risk are conflicting. In this meta-analysis, we aimed to investigate the association between HIF-1alpha 1772 C/T and 1790 G/A polymorphisms and cancer.<h4>Methods</h4>The meta-analysis for 1772 C/T polymorphism included 4131 cancer cases and 5387 controls, and for 1790 G/A polymorphism included 2058 cancer cases and 3026 controls. Allelic and ...[more]

PMID: 20035632

Similar Datasets

Project description:BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1alpha and HIF-1beta/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1alpha protein overexpression has been shown in breast cancer. The impact of HIF-1alpha alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known. METHODS: Using real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total HIF-1alpha and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers HIF-1alpha splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival. RESULTS: HIF-1alpha isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated HIF-1alphaTAG) and HIF-1alpha736 mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues (P = 0.009 and P = 0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with HIF-1alphaTAG mRNA levels (P = 0.037). Significant statistical association was found between tumour grade and HIF-1alphaTAG (P = 0.048), and total HIF-1alpha (P = 0.048) mRNA levels. HIF-1alphaTAG mRNA levels were also inversely correlated with both oestrogen and progesterone receptor status (P = 0.005 and P = 0.033 respectively). Univariate analysis showed that high HIF-1alphaTAG mRNA levels correlated with shortened metastasis free survival (P = 0.01). CONCLUSIONS: Our results show for the first time that mRNA expression of a HIF-1alphaTAG splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.See commentary: http://www.biomedcentral.com/1741-7015/8/45.

Project description:BACKGROUND:Hypoxia 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. METHODS:Meta-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. RESULTS:Meta-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. CONCLUSION:In 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.

Dataset Information

Hypoxia-inducible factor-1alpha gene polymorphisms and cancer risk: a meta-analysis.

Background

Methods

Results

Conclusions

Publications

Hypoxia-inducible factor-1alpha gene polymorphisms and cancer risk: a meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets