Dataset Information

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.

SUBMITTER: Lin S

PROVIDER: S-EPMC6322323 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Lin Shuchun S Liu Yun Y Goldin Lynn R LR Lyu Chen C Kong Xiangyin X Zhang Yan Y Caporaso Neil E NE Xiang Song S Gao Ying Y

Biology of sex differences 20190107 1

<h4>Background</h4>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.<h4>Methods</h4>Using the HumanMethylation450 BeadChip, we profiled the genome-wide DNA methylation pattern of CD19<sup>+</sup> B cells f ...[more]

PMID: 30616686

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Project description:ObjectivesTo characterize the impact of PCB exposure on DNA methylation in peripheral blood leucocytes and to evaluate the corresponding changes in relation to possible health effects, with a focus on B-cell lymphoma.MethodsWe conducted an epigenome-wide association study on 611 adults free of diagnosed disease, living in Italy and Sweden, in whom we also measured plasma concentrations of 6 PCB congeners, DDE and hexachlorobenzene.ResultsWe identified 650 CpG sites whose methylation correlates strongly (FDR < 0.01) with plasma concentrations of at least one PCB congener. Stronger effects were observed in males and in Sweden. This epigenetic exposure profile shows extensive and highly statistically significant overlaps with published profiles associated with the risk of future B-cell chronic lymphocytic leukemia (CLL) as well as with clinical CLL (38 and 28 CpG sites, respectively). For all these sites, the methylation changes were in the same direction for increasing exposure and for higher disease risk or clinical disease status, suggesting an etiological link between exposure and CLL. Mediation analysis reinforced the suggestion of a causal link between exposure, changes in DNA methylation and disease. Disease connectivity analysis identified multiple additional diseases associated with differentially methylated genes, including melanoma for which an etiological link with PCB exposure is established, as well as developmental and neurological diseases for which there is corresponding epidemiological evidence. Differentially methylated genes include many homeobox genes, suggesting that PCBs target stem cells. Furthermore, numerous polycomb protein target genes were hypermethylated with increasing exposure, an effect known to constitute an early marker of carcinogenesis.ConclusionsThis study provides mechanistic evidence in support of a link between exposure to PCBs and the etiology of CLL and underlines the utility of omic profiling in the evaluation of the potential toxicity of environmental chemicals.

Dataset Information

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

Publications

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

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