Meka Phanni Bhushann, Cingeetham Anuradha, Nanchari Santhoshi Rani, Damineni Surekha, Tipirisetti Nageshwarao, Gorre Manjula, Jarjapu Sarika, Annamaneni Sandhya, Digumarthi Raghunadharao, Satti Vishnupriya
Department of Genetics, Osmania University, Hyderabad, 500007, India.
Tumour Biol. 2015 May;36(5):3215-20. doi: 10.1007/s13277-014-2949-y. Epub 2014 Dec 16.
Hypoxia-inducible factor 1α (HIF-1α) is an important transcription factor that regulates different cellular responses to hypoxia. HIF-1α is rapidly degraded by von Hippel-Lindau (VHL) protein under normoxic conditions and stabilized under hypoxia. A common variant of HIF-1α (1772C>T) (rs 11549465) polymorphism, corresponding to an amino acid change from proline to serine at 582 position within the oxygen-dependent degradation domain, results in increased stability of the protein and altered transactivation of its target genes. The present study was aimed to find the association between HIF-1α (1772C>T) (rs 11549465) polymorphism and breast cancer development. For this purpose, 348 primary breast cancer patients and 320 healthy and age-matched controls were genotyped through PCR-RFLP method. The genotype frequencies were compared between patients and controls, and their influence on clinical characteristics of breast cancer patients was analyzed. Our study revealed a significant increase of TT genotype in breast cancer patients compared to controls (p = 0.038). Further, TT genotype and T allele were found to be associated with progesterone receptor (PR)-negative status (p < 0.09). None of the clinical variables revealed significant association with HIF-1α (1772C>T) (rs 11549465) polymorphism.
缺氧诱导因子1α（HIF-1α）是一种重要的转录因子，可调节细胞对缺氧的不同反应。在常氧条件下，HIF-1α会被冯·希佩尔-林道（VHL）蛋白迅速降解，而在缺氧条件下则会稳定下来。HIF-1α的一种常见变体（1772C>T）（rs 11549465）多态性，对应于氧依赖性降解结构域内第582位氨基酸从脯氨酸变为丝氨酸，导致该蛋白稳定性增加，其靶基因的反式激活发生改变。本研究旨在探讨HIF-1α（1772C>T）（rs 11549465）多态性与乳腺癌发生之间的关联。为此，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对348例原发性乳腺癌患者及320例年龄匹配的健康对照进行基因分型。比较患者与对照之间的基因型频率，并分析其对乳腺癌患者临床特征的影响。我们的研究显示，与对照组相比，乳腺癌患者中TT基因型显著增加（p = 0.038）。此外，发现TT基因型和T等位基因与孕激素受体（PR）阴性状态相关（p < 0.09）。没有任何临床变量显示与HIF-1α（1772C>T）（rs 11549465）多态性有显著关联。
