About LOY

LOY is a during lifetime acquired mutation occurring when the Y chromosome have been lost from a percentage of the peripheral blood cells. LOY is the most common human mutation and about 10%, 20% and more than 50% of men in the ages of 70, 80 and 90 years of age, have lost the entire Y chromosome in more than 10% of the blood cells.

LOY was first described more than 50 years ago and was long considered a neutral event related to normal aging. In contrast, recent results suggest that: men with detectable LOY in blood samples survives only half as long as age-matched controls!

LOY can therefore help explain why men in the entire world lives shorter lives compared to females. Furthermore, the list of diseases associated with LOY are constantly growing and so far, LOY in blood has been found to be associated with outcomes such as non-hematological cancer, prostate cancer, bladder cancer, colorectal cancer, testicular germ cell tumors, myelodysplastic syndrome, Alzheimer’s disease as well as major cardiovascular events.

LOY is more common in elderly men but it also occurs and associate with cancer risk in younger men. In addition to age, smoking and genetic background are known risk factors. Smokers risk are fourfold larger compared to non-smokers and GWAS have identified 19 inherited genetic variants increasing the risk to be affected by LOY.

How can LOY in blood cells increase the risk for disease in other organs and tissues? A likely explanation is that vital functions of immune cells in blood are compromized when affected with LOY. Ongoing research and preliminary data support this hypothesis. Regardless of the mechanism, LOY in blood could be used as a clinical biomarker to predict risk for various disease in middle-aged and elderly men.

Read more about these findings in these publications:

• Forsberg et al. Nature Genetics 2014. Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer (link)


• Dumanski et al. Science 2015. Mutagenesis. Smoking is associated with mosaic loss of chromosome Y (link)


• Ganster et al. Genes Chromosomes Cancer 2015. New data shed light on Y-loss-related pathogenesis in myelodysplastic syndromes (link)


• Noveski et al. PLoS One 2016. Loss of Y Chromosome in Peripheral Blood of Colorectal and Prostate Cancer Patients (link)


• Zhou et al. Nature Genetics 2016. Mosaic loss of chromosome Y is associated with common variation near TCL1A (link)


• Dumanski et al. American Journal of Human Genetics 2016. Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease (link)


• Forsberg Human Genetics 2017. Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men (link)


• Wright et al. Nature Genetics 2017. Genetic variants associated with mosaic Y chromosome loss highlight cell cycle genes and overlap with cancer susceptibility (link)


• Machiela et al. J Human Genetics 2017. Mosaic chromosome Y loss and testicular germ cell tumor risk (link)


• Haitjema et al. Circ Cardio Genet 2017. Loss of Y Chromosome in Blood Is Associated With Major Cardiovascular Events During Follow-Up in Men After Carotid Endarterectomy (link)


• Forsberg et al. Nature Reviews Genetics 2017. Mosaicism in health and disease - clones picking up speed (link)

About CRAY

BUSINESS IDEA: CRAY control IP-rights in the field of predicting increased risk for cancer and Alzheimer's disease by LOY-testing. The commercial applications are regulated in two patents granted by the European Patent Office (link). At this stage we are therefore open to commercial collaborations and partnerships.

HISTORY: CRAY Innovation AB (reg. # 556959-7510) was founded in 2014 as a result of the discovery that LOY in blood cells can be used to predict risk for all-cause mortality, cancer and Alzheimer's disease in men. CRAY is an abbreviation for Cancer Risk Assessment from loss of chromosome Y and was founded by Lars Forsberg (CEO) and Jan Dumanski, who both are scientists at Uppsala University. Later in 2014 industry experience was brought into the company when Mårten Winge (Chairman of the board) and Björn Ekstrom (board member) as well as Uppsala University Holding AB joined.

GOALS: The company’s ambition is to introduce LOY-tests as a new predictive biomarker in clinical genetics. To boost the clinical utility of LOY-testing we are developing the technology used for LOY detection. We are also describing the functional consequences of LOY in blood immune cells, which are likely leading to a reduced ability in men with LOY to fight various disease. Regardless of the causual mechanism, however, our studies show that LOY in blood cells can be used as a new, strong and predictive biomarker. In addition to predicting increased risk for cancer and Alzheimer's disease, numerous other clinical applications can be envisaged: a topic that CRAY aims to explore in the future.