Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
The MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Biol Sex Differ. 2019 Jan 7;10(1):2. doi: 10.1186/s13293-018-0213-7.
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.
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).
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.
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.
男性患慢性淋巴细胞白血病（CLL）的风险高于女性。DNA 甲基化在许多癌症中发挥着重要作用。男性和女性之间的 DNA 甲基化模式存在差异。在这项研究中，我们研究了这种差异是否导致了 B 细胞 CLL 风险的性别差异。
我们使用 HumanMethylation450 BeadChip 对 48 名 CLL 患者（29 名女性患者和 19 名男性患者）和 28 名健康人（19 名女性和 9 名男性）的 CD19 B 细胞进行了全基因组 DNA 甲基化谱分析。
我们确定了 1043 个与 CLL 相关的性别差异甲基化位置（DMPs），其中 56 个位于常染色体上，987 个位于 X 染色体上。使用已发表的 B 细胞 RNA 测序数据，我们发现 DMPs 覆盖的 18 个基因在男性和女性 CLL 患者中的表达水平也不同。其中，TRIB1 是一个常染色体基因，通过抑制细胞凋亡促进肿瘤生长。
我们的研究代表了首次对癌症中性别相关差异进行全基因组关联研究（EWAS）的研究，表明 DNA 甲基化差异可能导致 CLL 风险的性别差异。
