On average, men die earlier than women (1). Although differences in environmental, lifestyle, and exposure factors certainly explain some of the earlier mortality of men, recent population-based genomic investigations suggest somatic mutations could also influence this reduced overall life expectancy of men. In particular, an expanding body of evidence suggests somatic loss of the sex-determining Y chromosome, referred to as mosaic loss of Y (LOY), might be an important biomarker for elevated mortality rates among men, perhaps indirectly or through events on the Y chromosome itself (2,3). LOY is the most common copy number alteration in male leukocytes and is characterized by a mosaic mixture of normal cells with one copy of the Y chromosome and mutant cells with loss of the entire Y chromosome (4). LOY detected in peripheral leukocytes has been associated in early studies with hematologic malignancies (5,6) as well as nonhematologic disorders, including solid tumors, Alzheimer’s disease, and cardiovascular disease (2,7–11). However, further larger studies are needed to confirm these reports.

中文翻译：

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为什么是Y？染色体Y基因的下调可能导致癌症风险增加。

平均而言，男性死于女性（1）。尽管环境，生活方式和接触因素的差异确实可以解释男性早期死亡的原因，但最近基于人群的基因组研究表明，体细胞突变也可能影响男性预期寿命的缩短。特别是，越来越多的证据表明，决定性别的Y染色体的体细胞丢失，称为Y镶嵌丢失（LOY），可能是男性死亡率升高的重要生物标志物，可能是间接的或通过Y上的事件染色体本身（2,3）。LOY是雄性白细胞中最常见的拷贝数改变，其特征是正常细胞与Y染色体的一个拷贝与缺失整个Y染色体的突变细胞的镶嵌混合物（4）。在早期研究中，外周血白细胞中检测到的LOY与血液系统恶性肿瘤（5,6）以及非血液系统疾病（包括实体瘤，阿尔茨海默氏病和心血管疾病）[2,7-11]相关。但是，需要进一步更大的研究来确认这些报告。