Genetic variants in the histone methylation and acetylation
pathway and their risks in eight types of cancers
Lin Na FU,
Ying Xuan CHEN & Jing-Yuan FANG
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
OBJECTIVES: The histone methylation and acetyla-
tion pathway genes regulate cell growth and survival.
Aberrations in this pathway are implicated in a vari-
ety of cancers. This study aimed to identify germline
genetic variants in histone methylation and acetyla-
tion 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 asso-
ciations with eight types of cancers were analyzed
using logistic regression models and the
permutation-based adaptive rank-truncated product
RESULTS: Gene-level associations revealed that
genetic variants in 45 genes were signiﬁcantly associ-
ated with the risk of cancer. The total histone methyl-
ation 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), pan-
creatic (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. Fur-
ther studies are needed to validate these relations
and to explore relative mechanisms.
KEY WORDS: cancer, histone post-translational modiﬁcation, single nucleotide polymorphism.
The global cancer burden has continued to climb
over the past decade. The development of cancer is
thought to be a consequence of the accumulation of
Genome-wide association studies
evaluate genetic variants across the genome of differ-
ent individuals to discern whether any one variant is
related to a particular disease.
The relation between
single nucleotide polymorphisms (SNPs) and speciﬁc
human diseases like cancer is a major focus of
genome-wide association studies. However, the anal-
ysis of the associations of a single site can explain
Correspondence to: Ying Xuan CHEN, 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; 145 Middle Shandong Road, Shanghai
200001, China. Email: email@example.com
The authors have no conﬂict of interest to declare.
These authors contributed equally to this work.
Accepted for publication 29 December 2017.
© 2018 Chinese Medical Association Shanghai Branch, Chinese
Society of Gastroenterology, Renji Hospital Afﬁliated to Shanghai
Jiaotong University School of Medicine and John Wiley & Sons
Journal of Digestive Diseases 2018; 19; 102–111 doi: 10.1111/1751-2980.12574