Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
J Dig Dis. 2018 Feb;19(2):102-111. doi: 10.1111/1751-2980.12574.
The histone methylation and acetylation pathway genes regulate cell growth and survival. Aberrations in this pathway are implicated in a variety of cancers. This study aimed to identify germline genetic variants in histone methylation and acetylation pathway genes that may contribute to risk in eight types of cancers and to explore the relation between the whole pathway and their risks in these types of cancers.
Germline genetic variants in 89 genes in the histone methylation and acetylation pathway were explored. Gene-based and pathway-based associations with eight types of cancers were analyzed using logistic regression models and the permutation-based adaptive rank-truncated product method, respectively.
Gene-level associations revealed that genetic variants in 45 genes were significantly associated with the risk of cancer. The total histone methylation and acetylation pathway was significantly associated with the risk of esophageal squamous cell carcinoma (P = 0.0492) and prostate (P = 0.0038), lung (P = 0.00015), and bladder cancer (P = 0.00135), but not with breast (P = 0.182), pancreatic (P = 0.336) and gastric cancer (P = 0.347) and renal cell carcinoma (P =0.828).
Our study suggested there is an association between germline genetic variation at the overall histone methylation and acetylation pathway level and some individual genes with cancer risk. Further studies are needed to validate these relations and to explore relative mechanisms.
组蛋白甲基化和乙酰化途径基因调控细胞生长和存活。该途径的异常与多种癌症有关。本研究旨在鉴定组蛋白甲基化和乙酰化途径基因中的种系遗传变异，这些变异可能导致 8 种癌症的风险，并探讨整个途径及其在这些癌症类型中的风险之间的关系。
研究了组蛋白甲基化和乙酰化途径中 89 个基因的种系遗传变异。使用逻辑回归模型和基于置换的自适应秩截断乘积法分别分析了基于基因和基于途径的与 8 种癌症的关联。
基因水平的关联显示，45 个基因的遗传变异与癌症风险显著相关。总的组蛋白甲基化和乙酰化途径与食管鳞状细胞癌（P = 0.0492）、前列腺癌（P = 0.0038）、肺癌（P = 0.00015）和膀胱癌（P = 0.00135）的风险显著相关，但与乳腺癌（P = 0.182）、胰腺癌（P = 0.336）和胃癌（P = 0.347）以及肾细胞癌（P = 0.828）无关。
本研究表明，种系遗传变异与整体组蛋白甲基化和乙酰化途径水平以及某些个体基因与癌症风险之间存在关联。需要进一步的研究来验证这些关系并探索相关机制。
