Abstract
PurposeThe hypoxia-inducible factor-1 alpha (HIF1A) plays a vital role in cancer initiation and progression. Previous studies have reported the existence of HIF1A P582S and A588T missense polymorphisms in renal, urothelial and prostatic carcinomas, however the effects remain conflicting. Therefore, we performed a meta-analysis to assess the association between these sites and the susceptibility of urinary cancers.MethodsWe searched the PubMed database without limits on language until Nov 25, 2012 for studies exploring the relationship of HIF1A P582S and A588T polymorphisms and urinary cancers. Still, article search was supplemented by screening the references of retrieved studies manually. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the strength of the associations between the two by RevMan 5.0 software. Simultaneously, publication bias was estimated by funnel plot and Begg’s test with Stata 12.1 software.ResultsOverall, 11 individual case-control studies with 5195 cases and 5786 controls for P582S polymorphism, and 9 studies with 3482 cases and 4304 controls for A588T polymorphism were respectively included in the final meta-analysis. For HIF1A P582S polymorphism, individuals with TT genotype showed 1.60 fold higher risk than the others carrying CT or CC genotypes in Caucasian population (OR = 1.60, 95% CI = 1.09–2.33, P heterogeneity = 0.11, P = 0.02). For HIF1A A588T polymorphism, the A allele was significantly correlated with higher urinary cancers risk in Asian population (OR = 1.41, 95% CI = 1.03–1.93, P heterogeneity = 0.22, P = 0.03). Still, significant associations were found for prostate cancer in the allele and dominant models (OR = 1.46, 95% CI = 1.01–2.12, P heterogeneity = 0.49, P = 0.04 and OR = 1.45, 95% CI = 1.00–2.12, P heterogeneity = 0.50, P = 0.05).ConclusionsThe current findings suggest that HIF1A P582S polymorphism correlates with urinary cancers risk in Caucasian population, while A588T polymorphism may increase the risk of urinary cancers in Asian population and prostate cancer.
Highlights
Cancer, known as a malignant neoplasm, is involving in unregulated cell growth
The protein encoded by the hypoxia-inducible factor-1 alpha (HIF1A) gene is a key transcription factor found in cells growing at low oxygen concentrations, which regulates cellular responses, adaption and survival under hypoxia in physiology and pathological processes [3,4] via the increased transcription of several dozens of target genes (VEGF [5], DDX3 [6], iNOS [7], CX3CR1 [8], etc.)
We evaluated the contribution of HIF1A P582S and A588T polymorphisms to the risk of urinary cancers by adopting the RevMan software 5.0, which is developed by Cochrane Collaboration
Summary
Known as a malignant neoplasm, is involving in unregulated cell growth. Approximately 12.7 million cancers were newly diagnosed and 7.6 million people died of cancer worldwide [1]. The protein encoded by the hypoxia-inducible factor-1 alpha (HIF1A) gene is a key transcription factor found in cells growing at low oxygen concentrations, which regulates cellular responses, adaption and survival under hypoxia in physiology and pathological processes [3,4] via the increased transcription of several dozens of target genes (VEGF [5], DDX3 [6], iNOS [7], CX3CR1 [8], etc.) Both HIF1A and its encoding gene are supposed to be promising candidates in the pathogenesis of cancers [9]. Several studies done by other groups [11,15,18] failed to detect any association between HIF1A P582S and A588T polymorphisms and the risk of urinary cancers
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