Mol Diagn Ther. 2014 Feb;18(1):85-91. doi: 10.1007/s40291-013-0059-y.
The Wnt/β-catenin signaling pathway has been considered to be a factor in the development and progression of ovarian cancer.
All patients with ovarian cancer and controls were tested for BRCA1 mutations (5382incC, C61G, 4153delA) with HybProbe assays and for BRCA2 mutation (5946delT) using high-resolution melting curve analysis (HRM). Mutation carriers were excluded from the association analysis. We studied nine single nucleotide polymorphisms (SNPs) located in CTNNB1 (β-catenin) [rs4533622, rs2953], APC (rs11954856, rs351771, rs459552), and AXIN2 (rs4074947, rs7224837, rs3923087, rs2240308) in women with ovarian cancer without BRCA1/BRCA2 mutations (n = 228) and controls (n = 282). Genotyping of CTNNB1 rs4533622, rs2953, APC rs351771, AXIN2 rs4074947, rs3923087, and rs2240308 was performed by HRM, while that of APC rs11954856, rs459552 and AXIN2 rs7224837 was conducted by PCR followed by the appropriate restriction enzyme digestion [PCR–restriction fragment length polymorphism (PCR-RFLP)].
The most common BRCA1/BRCA2 mutations were identified in 30 patients with ovarian cancer. These mutations were not found in controls. The lowest p values of the trend test (p trend) were observed for the APC rs351771 and rs11954856 SNPs in patients with ovarian cancer (p trend = 0.006 and p trend = 0.007, respectively). Using a dominant inheritance model, we found that the APC rs11954856 SNP is associated with an increased risk of ovarian cancer development [odds ratio = 2.034 (95 % CI 1.302–3.178); p = 0.002]. We also observed significant allelic differences for the APC rs351771 SNP between patients and controls (p = 0.006).
Our study demonstrated significantly increased APC rs11954856 and rs351771 SNP frequencies in Polish women with ovarian cancer.
Wnt/β-catenin 信号通路被认为是卵巢癌发生和进展的一个因素。
所有卵巢癌患者和对照者均采用 HybProbe 检测进行 BRCA1 突变（5382incC、C61G、4153delA）检测，采用高分辨率熔解曲线分析（HRM）进行 BRCA2 突变（5946delT）检测。突变携带者被排除在关联分析之外。我们研究了位于 CTNNB1（β-连环蛋白）中的 9 个单核苷酸多态性（SNP）[rs4533622、rs2953]、APC（rs11954856、rs351771、rs459552）和 AXIN2（rs4074947、rs7224837、rs3923087、rs2240308），这些 SNP 在没有 BRCA1/BRCA2 突变的卵巢癌患者（n=228）和对照者（n=282）中进行了检测。采用 HRM 对 CTNNB1 rs4533622、rs2953、APC rs351771、AXIN2 rs4074947、rs3923087 和 rs2240308 进行基因分型，而 APC rs11954856、rs459552 和 AXIN2 rs7224837 则采用 PCR 后适当的限制性内切酶消化[PCR-限制性片段长度多态性（PCR-RFLP）]进行。
在 30 例卵巢癌患者中发现了最常见的 BRCA1/BRCA2 突变。这些突变在对照者中没有发现。在卵巢癌患者中，APC rs351771 和 rs11954856 SNP 的趋势检验（p 趋势）获得了最低的 p 值（p 趋势=0.006 和 p 趋势=0.007）。采用显性遗传模型，我们发现 APC rs11954856 SNP 与卵巢癌发生的风险增加相关[比值比=2.034（95%置信区间 1.302–3.178）；p=0.002]。我们还观察到 APC rs351771 SNP 在患者和对照者之间存在显著的等位基因差异（p=0.006）。
我们的研究表明，波兰妇女卵巢癌中 APC rs11954856 和 rs351771 SNP 频率显著增加。
