Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, United States.
Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20850, United States.
Hum Mol Genet. 2023 Nov 3;32(22):3146-3152. doi: 10.1093/hmg/ddad133.
Age-related clonal expansion of cells harbouring mosaic chromosomal alterations (mCAs) is one manifestation of clonal haematopoiesis. Identifying factors that influence the generation and promotion of clonal expansion of mCAs are key to investigate the role of mCAs in health and disease. Herein, we report on widely measured serum biomarkers and their possible association with mCAs, which could provide new insights into molecular alterations that promote acquisition and clonal expansion. We performed a cross-sectional investigation of the association of 32 widely measured serum biomarkers with autosomal mCAs, mosaic loss of the Y chromosome, and mosaic loss of the X chromosome in 436 784 cancer-free participants from the UK Biobank. mCAs were associated with a range of commonly measured serum biomarkers such as lipid levels, circulating sex hormones, blood sugar homeostasis, inflammation and immune function, vitamins and minerals, kidney function, and liver function. Biomarker levels in participants with mCAs were estimated to differ by up to 5% relative to mCA-free participants, and individuals with higher cell fraction mCAs had greater deviation in mean biomarker values. Polygenic scores associated with sex hormone binding globulin, vitamin D, and total cholesterol were also associated with mCAs. Overall, we observed commonly used clinical serum biomarkers related to disease risk are associated with mCAs, suggesting mechanisms involved in these diseases could be related to mCA proliferation and clonal expansion.
与携带嵌合染色体改变 (mCAs) 的细胞的年龄相关克隆扩张是克隆性造血的一种表现形式。确定影响 mCAs 产生和促进克隆扩张的因素是研究 mCAs 在健康和疾病中的作用的关键。在此，我们报告了广泛测量的血清生物标志物及其与 mCAs 的可能关联，这可能为促进获得和克隆扩张的分子改变提供新的见解。我们对来自英国生物库的 436784 名无癌症参与者的常染色体 mCAs、Y 染色体嵌合性缺失和 X 染色体嵌合性缺失与 32 种广泛测量的血清生物标志物之间的关联进行了横断面研究。mCAs 与多种常见的血清生物标志物相关，如血脂水平、循环性激素、血糖稳态、炎症和免疫功能、维生素和矿物质、肾功能和肝功能。与 mCA 无参与者相比，患有 mCAs 的参与者的生物标志物水平估计相差高达 5%，并且具有更高细胞分数 mCAs 的个体的平均生物标志物值偏差更大。与性激素结合球蛋白、维生素 D 和总胆固醇相关的多基因评分也与 mCAs 相关。总体而言，我们观察到与疾病风险相关的常用临床血清生物标志物与 mCAs 相关，这表明这些疾病中涉及的机制可能与 mCA 增殖和克隆扩张有关。
