The impact of mosaic loss of the Y chromosome (mLOY) in men of advanced age.

The Y chromosome has long been considered to be a "genetic wasteland" harboring only few genes essentially involved in male sex development and spermatogenesis. However, the discovery of mosaic loss of the Y chromosome (mLOY) in older men has led to revisiting of the potential impact of the Y chromosome on health and the pathophysiological processes of multiple diseases such as cancer, Alzheimer's disease and cardiovascular disease. Hence, developing more sensitive techniques for the detection of mLOY has become an emergent concern. In this article, we present a comprehensive review of the literature regarding mLOY. Additionally, we discuss the emerging discoveries concerning mLOY as well as the underlying mechanisms promoting disease in men of advanced age.

Abou Abdallah F ，Abdel Massih C ，Attieh C ，Chebly A ... -  《-》

Loss of the Y Chromosome: A Review of Molecular Mechanisms, Age Inference, and Implications for Men's Health.

Gutiérrez-Hurtado IA ，Sánchez-Méndez AD ，Becerra-Loaiza DS ，Rangel-Villalobos H ，Torres-Carrillo N ，Gallegos-Arreola MP ，Aguilar-Velázquez JA ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Evaluation of the usefulness of saliva for mosaic loss of chromosome Y analysis.

Hachiya T ，Kobayashi T ，Tsutae W ，Gan PHP ，Baran IS ，Horie S ... -  《Scientific Reports》

Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer's Disease Aetiopathogenesis in Men.

García-González P ，de Rojas I ，Moreno-Grau S ，Montrreal L ，Puerta R ，Alarcón-Martín E ，Quintela I ，Orellana A ，Andrade V ，Adami PVM ，Heilmann-Heimbach S ，Gomez-Garre P ，Periñán MT ，Alvarez I ，Diez-Fairen M ，Nuñez Llaves R ，Olivé Roig C ，Garcia-Ribas G ，Menéndez-González M ，Martínez C ，Aguilar M ，Buongiorno M ，Franco-Macías E ，Saez ME ，Cano A ，Bullido MJ ，Real LM ，Rodríguez-Rodríguez E ，Royo JL ，Álvarez V ，Pastor P ，Piñol-Ripoll G ，Mir P ，Lara MC ，Padilla MM ，Sánchez-Juan P ，Carracedo A ，Valero S ，Hernandez I ，Tàrraga L ，Ramirez A ，Boada M ，Ruiz A ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Mosaic Y Loss Is Moderately Associated with Solid Tumor Risk.

Mosaic loss of the Y chromosome (mLOY) in peripheral leukocytes is a somatic event in which a fraction of leukocytes have lost the entire Y chromosome. The frequency of mLOY increases with age and may reflect poor genomic maintenance as well as clonal imbalances in normal immune function, making mLOY an attractive candidate marker for cancer risk. Here, we investigated the relationship between mLOY and incident cancer in a large sample of 207,603 cancer-free men from the UK Biobank, in which 13,895 men developed an incident solid tumor during follow-up. We identified mLOY by scanning for deviations in genotyping array log R intensity ratios across the male-specific chromosome Y region. Overall, we detected low proportions of cells with mLOY in 3,358 (1.6%) men and high proportions of mLOY in 524 (0.3%) men. We found an association of mLOY with overall solid tumor incidence using both low and high mLOY thresholds [HRlow = 1.18; 95% confidence interval (CI)low, 1.07-1.30; P low = 0.001; HRhigh = 1.36; 95% CIhigh, 1.09-1.71; P high = 0.007] and more specifically we observed an association with lung cancer (HRhigh = 2.25; 95% CIhigh, 1.36-3.71; P high = 0.002). Stronger associations were observed without adjustment for smoking, suggesting that smoking is an important confounder of tumor incidence. It is unlikely that mLOY is a major mediator of the effect of cigarette smoking on cancer risk, as mLOY was observed in only a small fraction of smokers who developed cancer. In summary, mLOY was modestly associated with incidence of solid tumors in the UK Biobank, although for some cancer subtypes these findings may reflect residual confounding by smoking. SIGNIFICANCE: Evidence from the UK Biobank indicates mosaic chromosome Y loss in leukocytes is moderately associated with increased incidence of select solid tumors.

Loftfield E ，Zhou W ，Yeager M ，Chanock SJ ，Freedman ND ，Machiela MJ ... -  《-》