China-American Cancer Research Institute, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, China.
Key Laboratory for Epigenetics of Dongguan City, Dongguan, China.
Cancer Med. 2019 Apr;8(4):1893-1898. doi: 10.1002/cam4.2022. Epub 2019 Mar 23.
Our previous work reported activating transcription factor 1 (ATF1) is a promotive factor of nasopharyngeal carcinoma (NPC) tumorigenesis. This study is to further explore the association between the human ATF1 rs11169571 polymorphism and the risk of NPC occurrence. The association between ATF1 rs11169571 and risk of NPC occurrence was investigated in clinical samples of 560 patients and 661 controls obtained from southern China with high incidence of NPC. The genotypes were detected by PCR-RFLP. The differential expression activity of alleles -T and -C was analyzed with CNE-2 and C666-1 cells by luciferase reporter assay. Our data suggested that the allelic frequency and genotypes were significantly different between patients and controls. Compared to the TT homozygote, the TC and CC genotypes have been shown to be significantly decreased in NPC patients (OR = 0.494, 95% CI = 0.387-0.629, P < 0.001 and OR = 0.556, 95% CI = 0.364-0.851, P = 0.007, respectively). Compared to the -T allele, the -C allele is a factor of decreased risk in NPC (OR = 0.642, 95% CI = 0.537-0.767, P < 0.001). Luciferase reporter activity revealed that the -T allele confers a higher expression activity than the -C allele in CNE2 cells and C666-1 cells. In conclusion, ATF1 rs11169571 which could affect the expression of ATF1 is associated with NPC risk.
我们之前的工作报道激活转录因子 1(ATF1)是鼻咽癌(NPC)肿瘤发生的促进因素。本研究旨在进一步探讨人类 ATF1 rs11169571 多态性与 NPC 发生风险之间的关系。从中国南方 NPC 高发地区获得的 560 例患者和 661 例对照的临床样本中,通过 PCR-RFLP 检测 ATF1 rs11169571 与 NPC 发生风险的相关性。通过荧光素酶报告基因检测分析等位基因 -T 和 -C 的差异表达活性与 CNE-2 和 C666-1 细胞。我们的数据表明,患者和对照组之间的等位基因频率和基因型存在显著差异。与 TT 纯合子相比,TC 和 CC 基因型在 NPC 患者中明显降低(OR=0.494,95%CI=0.387-0.629,P<0.001 和 OR=0.556,95%CI=0.364-0.851,P=0.007)。与 -T 等位基因相比,-C 等位基因是 NPC 发病风险降低的因素(OR=0.642,95%CI=0.537-0.767,P<0.001)。荧光素酶报告基因活性显示,-T 等位基因在 CNE2 细胞和 C666-1 细胞中的表达活性高于 -C 等位基因。综上所述,ATF1 rs11169571 可能影响 ATF1 的表达,与 NPC 风险相关。