Genetic variants in the histone methylation and acetylation pathway and their risks in eight types of cancers

Abstract

Objectives: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: cancer; histone post-translational modification; single nucleotide polymorphism.