Abstract
BackgroundMen 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.MethodsUsing 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).ResultsWe 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.ConclusionsOur 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.
Highlights
Men are at higher risk of developing chronic lymphocytic leukemia (CLL) than women
Our study revealed a connection between the sex-related differences in DNA methylation and the CLL disease risk and outcome
A large number of X chromosomal sex-related differentially methylated positions (DMPs) were identified, and our data suggests that this is mainly contributed by X chromosome inactivation (XCI) escape of many X chromosomal genes in female CLL patients
Summary
Men are at higher risk of developing chronic lymphocytic leukemia (CLL) than women. There are differences in the DNA methylation pattern between men and women. We investigated whether this contributes to the sex-related difference of B cell CLL risk. Chronic lymphocytic leukemia (CLL) is characterized by proliferation and accumulation of malignant B lymphocytes in the peripheral lymphoid tissues and bone marrow. It is one of the most common leukemias among adults in the western world [1]. The Surveillance, Epidemiology, and End Results (SEER) database indicated that in 1975–2001, the US CLL incidence per 100,000 per year was 5.0 for men and 2.5 for women [3, 4]. Understanding the mechanism behind these sex-related differences will provide valuable insights into CLL
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