Functional repeats (TGYCC)n in the p53-inducible gene 3 (PIG3) promoter and susceptibility to squamous cell carcinoma of the head and neck
Functional repeats (TGYCC)n in the p53-inducible gene 3 (PIG3) promoter and susceptibility to squamous cell carcinoma of the head and neck
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DOI：
10.1093/carcin/bgs388
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发表时间：
2013-04-01
期刊：
影响因子：
4.7
通讯作者：
Wei, Qingyi
中科院分区：
文献类型：
--
作者：
Guan, Xiaoxiang;Liu, Zhensheng;Wei, Qingyi
p53-诱导基因3（PIG 3）启动子内的多态性五核苷酸微卫星序列（TGYCC）n与p53的转录激活程度相关，并被认为调节癌症的易感性。使用基于PCR银染的单链构象分析，我们可视化的PIG 3启动子（TGYCC）n基序的变异基因型在一个子集中的100个主题的四个种族：非西班牙裔白人，非洲裔美国人，西班牙裔美国人和中国原住民。我们发现PIG 3（TGYCC）（15）是最常见的等位基因，但在非西班牙裔白人中的频率（0.660）低于中国人（0.785）（P 0.016）。在另一项对616名头颈部鳞状细胞癌（SCCHN）患者和623名非西班牙裔白色人群的无癌对照的研究中，我们发现与PIG 3（TGYCC）（15）纯合子相比，无PIG 3（TGYCC）（15）等位基因的受试者具有显著增加的SCCHN风险[校正比值比（OR）1.34;杂合子的95%CI为1.041.73，变异纯合子的OR为1.69; 95%CI为1.182.44]，呈等位基因剂量反应方式（P 0.002）。随后的荧光素酶报告基因检测结果显示，野生型（TGYCC）（15）等位基因与其他（TGYCC）n基序相比具有最高的p53介导的转录活性。我们的数据表明，PIG 3变体多态性重复等位基因（TGYCC）（15）可能影响p53结合，因此可能是SCCHN易感性的标志物，但我们的发现需要在更大的研究中验证。
A polymorphic pentanucleotide microsatellite sequence (TGYCC)n within the p53-inducible gene 3 (PIG3) promoter is correlated with the extent of transcriptional activation by p53 and thought to modulate susceptibility to cancer. Using a PCRsilver staining-based single-strand conformation assay, we visualized variant genotypes of the PIG3 promoter (TGYCC)n motif in a subset of 100 subjects for each of four ethnic groups: non-Hispanic whites, African Americans, Hispanic Americans and Native Chinese. We found that PIG3 (TGYCC)(15) was the most common allele but less frequent in non-Hispanic whites (0.660) than in Chinese (0.785) (P 0.016). In an additional study of 616 patients with squamous cell carcinoma of the head and neck (SCCHN) and 623 cancer-free controls in a non-Hispanic white population, we found that compared with those who were PIG3 (TGYCC)(15) homozygotes, subjects without the PIG3 (TGYCC)(15) allele had a significantly increased SCCHN risk [adjusted odds ratio (OR) 1.34; 95% CI 1.041.73 for heterozygotes and OR 1.69; 95% CI 1.182.44 for variant homozygotes] in an allele-dose response manner (P 0.002). Consistently, subsequent luciferase reporter assay revealed that the wild-type (TGYCC)(15) allele had the highest p53-mediated transcriptional activity, compared with the other (TGYCC)n motifs. Our data suggest that the PIG3 variant polymorphic repeats alleles other than (TGYCC)(15) may affect p53 binding and thus may be a marker for susceptibility to SCCHN, but our findings need to be validated in larger studies.