Department of Otolaryngology and Immunology, Hillman Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
J Dent Res. 2011 Jun;90(6):740-6. doi: 10.1177/0022034511401622. Epub 2011 Mar 10.
Oral squamous cell carcinoma (OSCC) accounts for more than 90% of the malignant neoplasms that arise in the mucosa of the upper aerodigestive tract. Recent studies of cleft lip/palate have shown the association of genes involved in cancer. WNT pathway genes have been associated with several types of cancer and recently with cleft lip/palate. To investigate if genes associated with cleft lip/palate were also associated with oral cancer, we genotyped 188 individuals with OSCC and 225 control individuals for markers in AXIN2, AXIN1, GSK3β, WNT3A, WNT5A, WNT8A, WNT11, WNT3, and WNT9B. Statistical analysis was performed with PLINK 1.06 software to test for differences in allele frequencies of each polymorphism between cases and controls. We found association of SNPs in GSK3B (p = 0.0008) and WNT11 (p = 0.03) with OSCC. We also found overtransmission of GSK3B haplotypes in OSCC cases. Expression analyses showed up-regulation of WNT3A, GSK3B, and AXIN1 and down-regulation of WNT11 in OSCC in comparison with control tissues (P < 0.001). Additional studies should focus on the identification of potentially functional variants in these genes as contributors to human clefting and oral cancer.
口腔鳞状细胞癌 (OSCC) 占上呼吸道黏膜恶性肿瘤的 90%以上。最近对唇裂/腭裂的研究表明，癌症相关基因存在关联。WNT 通路基因与多种类型的癌症有关，最近与唇裂/腭裂有关。为了研究与唇裂/腭裂相关的基因是否也与口腔癌相关，我们对 188 名 OSCC 患者和 225 名对照个体的 AXIN2、AXIN1、GSK3β、WNT3A、WNT5A、WNT8A、WNT11、WNT3 和 WNT9B 标记物进行了基因分型。使用 PLINK 1.06 软件进行统计分析，以检验每个多态性在病例和对照组之间的等位基因频率差异。我们发现 GSK3B (p = 0.0008) 和 WNT11 (p = 0.03) 的 SNPs 与 OSCC 相关。我们还发现 OSCC 病例中 GSK3B 单倍型的过度传递。表达分析显示，与对照组织相比，OSCC 中 WNT3A、GSK3B 和 AXIN1 的表达上调，WNT11 的表达下调（P < 0.001）。进一步的研究应集中在鉴定这些基因中潜在的功能变体，作为人类唇裂和口腔癌的贡献因素。
