Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Harbin, Heilongjiang, People's Republic of China.
Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Street, Harbin, Heilongjiang, People's Republic of China.
Sci Rep. 2016 Jul 15;6:29869. doi: 10.1038/srep29869.
Given that E3 ubiquitin ligases (E3) regulate specific protein degradation in many cancer-related biological processes. E3 copy number variation (CNV) may affect the development and prognosis of colorectal cancer (CRC). Therefore, we detected CNVs of five E3 genes in 518 CRC patients and 518 age, gender and residence matched controls in China, and estimated the association between E3 gene CNVs and CRC risk and prognosis. We also estimated their interactions with environmental factors and CRC risk. We find a significant association between the CNVs of MDM2 and CRC risk (amp v.s. wt: odds ratio = 14.37, 95% confidence interval: 1.27, 163.74, P = 0.032), while SKP2 CNVs may significantly decrease CRC risk (del v.s. wt: odds ratio = 0.32, 95% confidence interval: 0.10, 1.00, P = 0.050). However, we find no significant association between the CNVs of other genes and CRC risk. The only significant gene-environment interaction effects are between SKP2 CNVs and consumption of fish and/or fruit (P = 0.014 and P = 0.035) and between FBXW7 CNVs and pork intake (P = 0.040). Finally, we find marginally significant association between β-TRCP CNVs and CRC prognosis (amp v.s. wt, hazard ratio = 0.42, 95% confidence interval: 0.19, 0.97, P = 0.050).
由于 E3 泛素连接酶（E3）在许多与癌症相关的生物过程中调节特定蛋白质的降解。E3 拷贝数变异（CNV）可能会影响结直肠癌（CRC）的发展和预后。因此，我们在中国检测了 518 例 CRC 患者和 518 例年龄、性别和居住地匹配的对照者的 5 种 E3 基因的 CNV，并估计了 E3 基因 CNV 与 CRC 风险和预后之间的关联。我们还估计了它们与环境因素和 CRC 风险的相互作用。我们发现 MDM2 的 CNV 与 CRC 风险之间存在显著关联（扩增与野生型相比：比值比=14.37，95%置信区间：1.27，163.74，P=0.032），而 SKP2 的 CNV 可能显著降低 CRC 风险（缺失与野生型相比：比值比=0.32，95%置信区间：0.10，1.00，P=0.050）。然而，我们发现其他基因的 CNV 与 CRC 风险之间没有显著关联。唯一显著的基因-环境相互作用效应是 SKP2 的 CNV 与鱼和/或水果的摄入（P=0.014 和 P=0.035）和 FBXW7 的 CNV 与猪肉摄入之间（P=0.040）。最后，我们发现β-TRCP 的 CNV 与 CRC 的预后之间存在显著关联（扩增与野生型相比，风险比=0.42，95%置信区间：0.19，0.97，P=0.050）。
