Tan Juan, Yu Chen-Yang, Wang Zhen-Hua, Chen Hao-Yan, Guan Jian, Chen Ying-Xuan, Fang Jing-Yuan
State Key Laboratory of Oncogene and Related Genes, Key Laboratory of Gastroenterology &Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institution of Digestive Disease, 145 Middle Shandong Rd, Shanghai 200001, China.
Department of Otolaryngology, The Affiliated Sixth People's Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai 200233, China.
Sci Rep. 2015 Feb 16;5:8473. doi: 10.1038/srep08473.
Members of the inositol phosphate metabolism pathway regulate cell proliferation, migration and phosphatidylinositol-3-kinase (PI3K)/Akt signaling, and are frequently dysregulated in cancer. Whether germline genetic variants in inositol phosphate metabolism pathway are associated with cancer risk remains to be clarified. We examined the association between inositol phosphate metabolism pathway genes and risk of eight types of cancer using data from genome-wide association studies. Logistic regression models were applied to evaluate SNP-level associations. Gene- and pathway-based associations were tested using the permutation-based adaptive rank-truncated product method. The overall inositol phosphate metabolism pathway was significantly associated with risk of lung cancer (P = 2.00 × 10(-4)), esophageal squamous cell carcinoma (P = 5.70 × 10(-3)), gastric cancer (P = 3.03 × 10(-2)) and renal cell carcinoma (P = 1.26 × 10(-2)), but not with pancreatic cancer (P = 1.40 × 10(-1)), breast cancer (P = 3.03 × 10(-1)), prostate cancer (P = 4.51 × 10(-1)), and bladder cancer (P = 6.30 × 10(-1)). Our results provide a link between inherited variation in the overall inositol phosphate metabolism pathway and several individual genes and cancer. Further studies will be needed to validate these positive findings, and to explore its mechanisms.
肌醇磷酸代谢途径的成员调节细胞增殖、迁移以及磷脂酰肌醇-3-激酶（PI3K）/Akt信号传导，并且在癌症中经常失调。肌醇磷酸代谢途径中的种系基因变异是否与癌症风险相关仍有待阐明。我们使用全基因组关联研究的数据，研究了肌醇磷酸代谢途径基因与八种癌症风险之间的关联。应用逻辑回归模型评估单核苷酸多态性（SNP）水平的关联。基于基因和途径的关联使用基于置换的自适应秩截断乘积法进行检验。整个肌醇磷酸代谢途径与肺癌风险（P = 2.00×10⁻⁴）、食管鳞状细胞癌风险（P = 5.70×10⁻³）、胃癌风险（P = 3.03×10⁻²）和肾细胞癌风险（P = 1.26×10⁻²）显著相关，但与胰腺癌风险（P = 1.40×10⁻¹）、乳腺癌风险（P = 3.03×10⁻¹）、前列腺癌风险（P = 4.51×10⁻¹）和膀胱癌风险（P = 6.30×10⁻¹）无关。我们的研究结果揭示了整个肌醇磷酸代谢途径中的遗传变异与几个单个基因和癌症之间的联系。需要进一步的研究来验证这些阳性发现，并探索其机制。
