Prince Fahd Bin Sultan Research Chair, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.
Endocr Metab Immune Disord Drug Targets. 2021;21(3):544-553. doi: 10.2174/1871530320666200910105214.
Hypoxia-inducible factor 1 (HIF-1α) is responsible in regulating oxygen homeostasis in tissues and is a central effector of the hypoxic response besides its protein overexpression has been shown to have prognostic relevance in several cancers including breast cancer. Several reports indicated that HIF-1α gene variation C1772T (Pro582Ser) is associated with increased breast susceptibility but results remained controversial. Therefore, we performed the molecular evaluation of HIF-1α gene variation and determined its frequency and association with Breast Cancer susceptibility in Saudi Arabia.
This study was conducted on histologically confirmed Breast cancer patients and gender matched healthy women. HIF-1α C1772T (Pro582Ser) genotyping was done by Amplification refractory mutation system PCR method. The HIF-1α gene genotypes were correlated with different clinicopathological characteristics of breast cancer patients.
A significant difference was observed in genotype distribution of HIF-1α gene variation C1772T (Pro582Ser) between breast cancer cases and gender matched healthy controls (P=0.010). Our findings showed that the HIF- 1α variant was associated with an increased risk of Breast cancer for HIF-1α CC vs CT genotype OR = 2.20, 95% CI = (1.28 -3.77), P = 0.004) in codominant inheritance model. The significant association was reported for HIF1A for genotypes CC vs (CT+ TT) OR = 1.98, 95% CI = (1.17-3.34), P = 0.010) in dominant inheritance model tested. In case of recessive inheritance model, a non-significant association of HIF-1 alpha gene variants was reported for (CC+ CT) vs TT) OR = 1.03, 95% CI = (0. 064-16.79), P = 0.97). During the allelic comparison, a non-significant association was reported between A vs C allele among Breast cancer patients. A significant association of HIF- 1α polymorphism was reported with stage as well as distant metastasis of the disease.
A significant difference was observed in genotype distribution of HIF-1α gene variation C1772T (Pro>Ser) between breast cancer cases and gene matched healthy controls (P=0.010). HIF-1α- CT heterozygosity and CC genotype increased the susceptibility .The HIF-1α polymorphism was reported to be significantly associated with the distant metastasis of Breast cancer. Further studies with larger data set and well-designed models are required to validate our findings.
缺氧诱导因子 1（HIF-1α）负责调节组织中的氧稳态，是缺氧反应的中心效应物，其蛋白过表达已被证明与包括乳腺癌在内的几种癌症的预后相关。有几项报告表明，HIF-1α 基因变异 C1772T（脯氨酸 582 丝氨酸）与增加的乳腺癌易感性有关，但结果仍存在争议。因此，我们对 HIF-1α 基因变异进行了分子评估，并确定了其在沙特阿拉伯的乳腺癌易感性中的频率和相关性。
本研究对组织学证实的乳腺癌患者和性别匹配的健康女性进行了研究。采用扩增受阻突变系统 PCR 法对 HIF-1α C1772T（脯氨酸 582 丝氨酸）进行基因分型。将 HIF-1α 基因基因型与乳腺癌患者的不同临床病理特征相关联。
乳腺癌病例与性别匹配的健康对照组之间 HIF-1α 基因变异 C1772T（脯氨酸 582 丝氨酸）的基因型分布存在显著差异（P=0.010）。我们的研究结果表明，HIF-1α 变体与乳腺癌风险增加相关，对于 HIF-1α CC 与 CT 基因型，OR=2.20，95%CI=（1.28-3.77），P=0.004）在共显性遗传模型中。在显性遗传模型中，报告了 HIF1A 基因型 CC 与（CT+TT）的显著关联，OR=1.98，95%CI=（1.17-3.34），P=0.010）。在隐性遗传模型中，报告了 HIF-1α 基因变异的非显著关联（CC+CT）与 TT）OR=1.03，95%CI=（0.064-16.79），P=0.97）。在等位基因比较中，在乳腺癌患者中，A 与 C 等位基因之间没有报告显著关联。HIF-1α 多态性与疾病的分期和远处转移有显著关联。
乳腺癌病例与基因匹配的健康对照组之间 HIF-1α 基因变异 C1772T（脯氨酸 582 丝氨酸）的基因型分布存在显著差异（P=0.010）。HIF-1α-CT 杂合性和 CC 基因型增加了易感性。HIF-1α 多态性与乳腺癌的远处转移显著相关。需要进一步的研究，包括更大的数据集和精心设计的模型，以验证我们的发现。
