State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Asian J Androl. 2012 Nov;14(6):864-9. doi: 10.1038/aja.2012.101. Epub 2012 Oct 8.
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.
缺氧诱导因子-1α（HIF-1α）在调节血管生成中发挥重要作用，而血管生成是肿瘤生长和转移所必需的。已经表明，HIF1A（编码 HIF-1α）的遗传变异会影响个体对许多人类肿瘤的易感性；然而，关于 HIF1A 单核苷酸多态性（SNP）与前列腺癌（PCa）风险之间关联的证据存在冲突。我们使用 TaqMan 方法对 HIF1A 中的三个潜在功能 SNP（rs11549465、rs11549467 和 rs2057482）进行基因分型，并在中国汉族人群中对 662 例 PCa 患者和 716 例对照进行病例对照研究，评估它们与 PCa 风险的关联。与 rs11549467 GG 基因型相比，变异基因型 GA+AA 显著增加了 PCa 风险（调整后的优势比（OR）=1.70；95%置信区间（CI）=1.06-2.72），尤其是在年龄较大的患者（OR=2.01；95%CI=1.05-3.86）、吸烟者（OR=2.06；95%CI=1.07-3.99）、从不饮酒者（OR=2.16；95%CI=1.20-3.86）和没有癌症家族史的患者（OR=1.71；95%CI=1.02-2.89）中。此外，携带 rs11549467 变异基因型的患者与更高的 Gleason 评分相关（OR=2.14；95%CI=1.22-3.75）。rs11549465 和 rs2057482 多态性与 PCa 风险无改变相关。然而，rs2057482 和 rs11549467 的组合变异基因型与 PCa 风险增加相关（在携带三个或更多风险等位基因的受试者中，OR=2.10；95%CI=1.23-3.57）。这些结果表明，HIF1A 多态性可能影响中国汉族人群的 PCa 易感性和进展。
