Genetic polymorphisms in HIF1A are associated with prostate cancer risk in a Chinese population

Abstract

The hypoxia-inducible factor-1α (HIF-1α) plays an important role in regulating angiogenesis, which is essential for tumor growth and metastasis. Genetic variations of HIF1A (coding HIF-1α) have been shown to influence an individual's susceptibility to many human tumors; however, evidence on associations between HIF1A single-nucleotide polymorphisms (SNPs) and prostate cancer (PCa) risk is conflicting. We genotyped three potentially functional polymorphisms in HIF1A (rs11549465, rs11549467 and rs2057482) using the TaqMan method and assessed their associations with PCa risk in a case-control study of 662 PCa patients and 716 controls in a Chinese Han population. Compared with rs11549467 GG genotype, the variant genotypes GA+AA had a significantly increased PCa risk (adjusted odds ratio (OR)=1.70; 95% confidence interval (CI)=1.06-2.72), particularly among older patients (OR=2.01; 95%CI=1.05-3.86), smokers (OR=2.06; 95%CI=1.07-3.99), never drinkers (OR=2.16; 95%CI=1.20-3.86) and patients without a family history of cancer (OR=1.71; 95%CI=1.02-2.89). Furthermore, patients with rs11549467 variant genotypes were associated with a higher Gleason score (OR=2.14; 95%CI=1.22-3.75). No altered PCa risk was associated with the rs11549465 and rs2057482 polymorphism. However, the combined variant genotypes of rs2057482 and rs11549467 were associated with increased PCa risk (OR=2.10; 95%CI=1.23-3.57 among subjects carrying three or more risk alleles). These results suggest that HIF1A polymorphisms may impact PCa susceptibility and progression in the Chinese Han population.

Genetic Variations in the HIF1A Gene Modulate Response to Adjuvant Chemotherapy after Surgery in Patients with Colorectal Cancer

“…In another case-control study, they have observed the significant associations of SNP rs2057482 with risk of rectal cancer (Frank et al, 2010). In addition, another study has demonstrated that the combined variant genotypes of rs2057482 and rs11549467 are associated with increased prostate cancer risk (Li et al, 2012). However, hardly any studies have been performed to find the association between SNP rs2301113 and cancers.…”

HIF1α Genetic Variants and Protein Expressions Determine the Response to Platinum Based Chemotherapy and Clinical Outcome in Patients with Advanced NSCLC

“…Recently, two polymorphisms, namely, the C1772T (P582S) and G1790A (A588T) polymorphisms of the HIF-1α gene have been reported to significantly increase gene transcriptional activity, leading to an increased expression of HIF-1α mRNA and protein [27,28]. …”

The HIF1A functional genetic polymorphism at locus +1772 associates with progression to metastatic prostate cancer and refractoriness to hormonal castration

“…We analysed a functional SNP (+1772 C>T) in the HIF1A gene in prostate cancer patients and controls and found lack of association, although a relatively large population with approximately 1500 men was analysed. Concordantly, two large case-control studies from the United States of America and China also observed no risk for having PCa in carriers of this polymorphism [19,26], even though opposite results have been also reported [16,27]. The C-by-T substitution in the +1772 locus at the oxygen-dependent domain of the HIF1A gene results in a proline-to-serine substitution and was shown to stabilise HIF1A and enhance its activity as a transcription factor in both normoxia and hypoxia [12,28].…”