Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Cancer Biol Ther. 2011 Sep 1;12(5):383-7. doi: 10.4161/cbt.12.5.15982.
The transcription factor hypoxia-inducible factor-1 (HIF-1) has α and β subunits. Recent studies have shown that the HIF-1α gene may have C1772T and G1790A single nucleotide polymorphisms (SNPs). These SNPs may increase the stability and activity of HIF-1α. In the present study, we looked for these SNPs by genotyping circulating mononuclear cells from 263 patients with pancreatic ductal adenocarcinoma (PDAC), using 271 healthy volunteers as controls. As a result, both SNPs were more frequent in PDAC patients than in healthy volunteers (C1772T: 21 vs. 11%, p < 0.01; G1790A: 25 vs. 8%, p < 0.01). Further, both SNPs were associated with higher risks for PDAC (C1772T: OR=2.156, 95% CI: 1.324-3.511, p < 0.05; G1790A: OR=3.716, 95% CI: 2.213-6.238, p < 0.01). We also stained HIF-1α by immunohistochemistry in 68 PDAC tumors to examine their HIF-1α expression levels. To this end, we designed a semi-quantitative method that was based on the staining intensity and frequency of HIF-1α-positive cells. As a result, the G1790A SNP, but not C1772T SNP, was associated with an increased HIF-1α expression. We also related genotyping data to patient's survival times, serum CA19-9, and tumor's volumes, grades, stages and lymph-node metastasis. The C1772T SNP was not associated with any of these parameters. In contrast, the G1790A SNP was associated with increases in serum CA19-9 and in tumor volumes. In conclusion, the C1772T and G1790A SNPs in the HIF-1α gene increase the susceptibility to pancreatic cancer. In addition, the G1790A SNP is associated with increases in tumor-produced HIF-1α and in the progression of the cancer.
转录因子缺氧诱导因子-1（HIF-1）具有α和β亚基。最近的研究表明，HIF-1α基因可能具有 C1772T 和 G1790A 单核苷酸多态性（SNP）。这些 SNP 可能会增加 HIF-1α的稳定性和活性。在本研究中，我们通过对 263 例胰腺导管腺癌（PDAC）患者的循环单核细胞进行基因分型，寻找这些 SNP，以 271 名健康志愿者作为对照。结果，C1772T（21%比 11%，p < 0.01）和 G1790A（25%比 8%，p < 0.01）两种 SNP 在 PDAC 患者中均比健康志愿者更常见。此外，两种 SNP 均与 PDAC 的高风险相关（C1772T：OR=2.156，95%CI：1.324-3.511，p < 0.05；G1790A：OR=3.716，95%CI：2.213-6.238，p < 0.01）。我们还通过免疫组织化学法对 68 例 PDAC 肿瘤中的 HIF-1α进行了染色，以检测其 HIF-1α表达水平。为此，我们设计了一种基于 HIF-1α阳性细胞的染色强度和频率的半定量方法。结果表明，G1790A SNP 而不是 C1772T SNP 与 HIF-1α表达的增加有关。我们还将基因分型数据与患者的生存时间、血清 CA19-9 和肿瘤体积、分级、分期和淋巴结转移相关联。C1772T SNP 与这些参数均无相关性。相比之下，G1790A SNP 与血清 CA19-9 和肿瘤体积的增加有关。结论：HIF-1α基因中的 C1772T 和 G1790A SNP 增加了患胰腺癌的易感性。此外，G1790A SNP 与肿瘤产生的 HIF-1α增加和癌症的进展有关。
