Gao Yan, Tang Xiuwu, Cao Jieqin, Rong Rong, Yu Zhengmin, Liu Yang, Lu Yan, Liu Xiaowen, Han Lei, Liu Jiting, Zhang Jun, Xu Ming, Liu Fang
Institute of Suzhou Biobank, Suzhou Center for Disease Prevention andControl, Suzhou 215004, China.
School of Public Health, Medical College of Soochow University, Suzhou 215123, China.
J Cancer. 2019 Jan 1;10(2):378-387. doi: 10.7150/jca.27976. eCollection 2019.
Cervical cancer (CCa) is a multifactorial gynecologic disease worldwide. Effects of polymorphisms, especially those in exonic region, have been investigated in many gynecologic diseases. In this study, we evaluated the influence of functional polymorphisms on susceptibility and survival of CCa in a Chinese population. We genotyped the HER2 exonic polymorphisms by TaqMan in both case-control study (413 CCa patients vs. 396 controls) and survival study (413 CCa patients). Logistic regression and Cox regression were adopted to evaluate the genetic association with the risk and outcomes of CCa, respectively. In the case-control study, there was no significant difference between patients and controls in either rs1136201 or rs1058808. However, when combined, these two polymorphisms demonstrated a significant hazardous effect for CCa ( = 0.012). Besides, number of variants was also influential ( trend =0.002). In survival analysis, dominant model of rs1136201 and co-dominant modelof rs1058808 were significantly associated with the survival ( = 0.037 and =0.028). The combination of rs1136201 and rs1058808 also negatively impacted CCa survival ( = 0.009). Cox regression further revealed the significance of the polymorphism combination (β = 0.38, = 0.025, HR= 1.47, 95%CI = 1.05-2.05). Functional assay of these polymorphisms demonstrated that rs1058808 G allele was associated with stronger expression of gene. Our results suggested that the combination of rs1136201and rs1058808 was significantly associated with the susceptibility of CCa. Besides, this combination of polymorphism s also substantially impacted the survival of CCa patients.
宫颈癌（CCa）是一种全球范围内的多因素妇科疾病。多态性的影响，尤其是外显子区域的多态性，已在许多妇科疾病中得到研究。在本研究中，我们评估了功能多态性对中国人群中CCa易感性和生存率的影响。我们在病例对照研究（413例CCa患者与396例对照）和生存研究（413例CCa患者）中通过TaqMan对HER2外显子多态性进行基因分型。采用逻辑回归和Cox回归分别评估与CCa风险和结局的遗传关联。在病例对照研究中，rs1136201或rs1058808在患者和对照之间均无显著差异。然而，当两者结合时，这两种多态性对CCa显示出显著的有害作用（P = 0.012）。此外，变异数量也有影响（P趋势 = 0.002）。在生存分析中，rs1136201的显性模型和rs1058808的共显性模型与生存率显著相关（P = 0.037和P = 0.028）。rs1136201和rs1058808的组合也对CCa生存产生负面影响（P = 0.009）。Cox回归进一步揭示了多态性组合的显著性（β = 0.38，P = 0.025，HR = 1.47，95%CI = 1.05 - 2.05）。这些多态性的功能分析表明，rs1058808 G等位基因与基因的更强表达相关。我们的结果表明，rs1136201和rs1058808的组合与CCa的易感性显著相关。此外，这种多态性组合也对CCa患者的生存产生了实质性影响。
