Konac Ece, Onen H Ilke, Metindir Jale, Alp Ebru, Biri Aydan Asyali, Ekmekci Abdullah
Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, 06500 Besevler, Ankara, Turkey.
Cancer Detect Prev. 2007;31(2):102-9. doi: 10.1016/j.cdp.2007.01.001. Epub 2007 Apr 6.
DNA sequence variations in HIF-1 alpha gene might yield changes both in the production outcomes and in the activities of the gene. Overexpression of the HIF-1 alpha subunit, resulting from intratumoral hypoxia and genetic alterations, has been demonstrated in common human cancers and is correlated with tumor angiogenesis and patient mortality. In this study, we aimed to determine how the three single nucleotide polymorphisms (SNPs, C1772T and G1790A exon 12, C111A exon 2) in the HIF-1 alpha gene coding regions affect the ovarian, cervical and endometrial cancer patients in the Turkish population. A study on this relationship has not been conducted to date.
102 gynecologic cancer patients and 107 healthy controls were studied. Genotypes of the three polymorphisms were analyzed by PCR-RFLP.
There was no significant difference between ovarian cancer patients and controls in terms of the distribution of C1772T genotypes and alleles (P>0.05). However, there was a highly significant increase in the frequency of both CT 1772 and TT 1772 genotypes in patients with cervical and endometrial cancers compared with healthy controls. In fact, 1772T allele-carriers (CT+TT genotypes) showed an association with the risk of cervical and endometrial cancers compared to the wild type (OR=3.84, 95% CI: 1.65-8.93; OR=7.41, 95% CI: 2.33-23.59, respectively). C1772T polymorphism was not associated with family history concerning gynecologic and/or other cancer types, stages (I-IV) and grades of tumor, smoking habits and existence of other diseases that generate a hypoxic microenvironment even after multivariable logistic regression analysis. As for HIF-1 alpha G1790A genotypes, the frequencies of G alleles were 98% in ovarian patients and 100% in the control group. We found no significant difference in the genotype distribution and allele frequencies between the ovarian patients and healthy control subjects. There were no GA and AA genotypes among the cervical and endometrial cancer patients. As for HIF-1 alpha C111A polymorphism, we did not find CA and AA variants of the gene in controls or in any of the three types of patients.
Our results suggest that the C1772T polymorphism of the HIF-1 alpha may be associated with cervical and endometrial cancers.
缺氧诱导因子-1α（HIF-1α）基因的DNA序列变异可能导致该基因的产生结果和活性发生变化。肿瘤内缺氧和基因改变导致的HIF-1α亚基过表达已在常见人类癌症中得到证实，并且与肿瘤血管生成和患者死亡率相关。在本研究中，我们旨在确定HIF-1α基因编码区的三个单核苷酸多态性（SNP，第12外显子的C1772T和G1790A，第2外显子的C111A）如何影响土耳其人群中的卵巢癌、宫颈癌和子宫内膜癌患者。迄今为止尚未开展关于这种关系的研究。
对102例妇科癌症患者和107例健康对照者进行研究。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析这三个多态性的基因型。
在C1772T基因型和等位基因的分布方面，卵巢癌患者与对照组之间无显著差异（P>0.05）。然而，与健康对照相比，宫颈癌和子宫内膜癌患者中CT 1772和TT 1772基因型的频率均显著增加。事实上，与野生型相比，1772T等位基因携带者（CT+TT基因型）显示出与宫颈癌和子宫内膜癌风险相关（OR=3.84，95%可信区间：1.65-8.93；OR=7.41，95%可信区间：2.33-23.59）。即使经过多变量逻辑回归分析，C1772T多态性也与妇科和/或其他癌症类型的家族史、肿瘤分期（I-IV期）和分级、吸烟习惯以及产生缺氧微环境的其他疾病的存在无关。至于HIF-1α G1790A基因型，卵巢癌患者中G等位基因的频率为98%，对照组中为100%。我们发现卵巢癌患者与健康对照受试者之间的基因型分布和等位基因频率无显著差异。宫颈癌和子宫内膜癌患者中不存在GA和AA基因型。至于HIF-1α C111A多态性，我们在对照组或任何一种类型的患者中均未发现该基因的CA和AA变体。
我们的结果表明，HIF-1α的C1772T多态性可能与宫颈癌和子宫内膜癌相关。
