Polymorphism in the hypoxia-inducible factor 1α gene may confer susceptibility to androgen-independent prostate cancer
Polymorphism in the hypoxia-inducible factor 1α gene may confer susceptibility to androgen-independent prostate cancer
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DOI：
10.4161/cbt.4.11.2091
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发表时间：
2005-11-01
影响因子：
3.6
通讯作者：
Figg, WD
中科院分区：
文献类型：
--
作者：
Chau, CH;Permenter, MG;Figg, WD
缺氧诱导因子1 α (HIF-1 α)在癌症进展中起着重要作用。这种转录因子在前列腺癌的发展及其向转移和雄激素难治性状态的转变中的作用仍有待阐明。先前的报道已经发现，在肾细胞癌、头颈部鳞状细胞癌和雄激素非依赖性前列腺癌（AIPC）中，HIF-1 α基因的氧依赖降解区域存在单核苷酸多态性（snp）。然而，前列腺癌的研究在评估的病例数量上是可变的和有限的。在这里，我们进一步研究了这些snp，特别是C1772T（导致氨基酸从脯氨酸582变为丝氨酸）和G1790A（丙氨酸588变为苏氨酸）。这些多态性的频率在转移性AIPC个体群体中进行了评估，并与一组健康对照受试者进行了比较。196例AIPC患者C1772T HIF-1 α基因型分布分别为161 C/C（82.1%）、29 C/T（14.8%）和6 T/T（3.1%）。196例对照的基因型分布分别为179 C/C（91.3%）、14 C/T（7.1%）和3 T/T（1.5%）。结果表明，AIPC患者与对照组的基因型分布仅在C1772T多态性上存在显著差异（p = 0.024）。通过Mantel-Haenszel （log-rank）检验确定多态性发生率与总生存率的相关性无统计学意义（p = 0.93）。这些结果表明，HIF-1 α的C1772T多态性可能与AIPC易感性有关，并有助于该疾病的进展或转移。
The hypoxia-inducible factor 1 alpha ( HIF-1 alpha) plays a major role in cancer progression. The role of this transcription factor in prostate cancer development and its transition to a metastatic and androgen refractory state remains to be elucidated. Previous reports have identified the existence of single nucleotide polymorphisms ( SNPs) in the oxygen-dependent degradation domain of the HIF-1 alpha gene in renal cell carcinoma, head and neck squamous cell carcinoma, and androgen-independent prostate cancer ( AIPC). Studies in prostate cancer, however, are variable and limited in the number of cases assessed. Herein we further investigate these SNPs, specifically C1772T ( which results in an amino acid change from proline 582 to serine) and G1790A ( alanine 588 to threonine). The frequency of these polymorphisms was evaluated in a population of individuals with metastatic AIPC and compared to a set of healthy control subjects. The distribution of HIF-1 alpha genotypes for C1772T in 196 AIPC patients was 161 C/C ( 82.1%), 29 C/T ( 14.8%), and 6 T/T ( 3.1%). The genotype distribution in 196 controls was 179 C/C ( 91.3%), 14 C/T ( 7.1%), and 3 T/T ( 1.5%). Our results demonstrate a significant difference in genotype distribution between AIPC patients and control subjects only for the C1772T polymorphism ( p = 0.024). The association of the incidence of the polymorphism with overall survival was determined to be not statistically significant ( p = 0.93) by the Mantel-Haenszel ( log-rank) test. These results suggest that the C1772T polymorphism in HIF-1 alpha may confer susceptibility to AIPC and contribute to the progression or metastasis of this disease.