Sex-related DNA methylation differences in B cell chronic lymphocytic leukemia

Abstract

Background

Men are at higher risk of developing chronic lymphocytic leukemia (CLL) than women. DNA methylation has been shown to play important roles in a number of cancers. There are differences in the DNA methylation pattern between men and women. In this study, we investigated whether this contributes to the sex-related difference of B cell CLL risk.

Methods

Using the HumanMethylation450 BeadChip, we profiled the genome-wide DNA methylation pattern of CD19⁺ B cells from 48 CLL patients (29 female patients and 19 male patients) and 28 healthy people (19 women and 9 men).

Results

We identified 1043 sex-related differentially methylated positions (DMPs) related to CLL, 56 of which are located on autosomes and 987 on the X chromosome. Using published B cell RNA-sequencing data, we found 18 genes covered by the DMPs also have different expression levels in male and female CLL patients. Among them, TRIB1, an autosome gene, has been shown to promote tumor growth by suppressing apoptosis.

Conclusions

Our study represents the first epigenome-wide association study (EWAS) that investigates the sex-related differences in cancer, and indicated that DNA methylation differences might contribute to the sex-related difference in CLL risk.