Credit: Pasieka / Science Source

Men are at a higher risk of developing and dying from sex-nonspecific cancers, but the reasons for this are unknown. A recent study with more than 1,000 adult men shows that the mosaic loss of chromosome Y (LOY) in peripheral blood cells may explain this increased cancer risk and related deaths in men (Nat. Genet. doi:10.1038/ng.2966, 2014).

Lars Forsberg and his colleagues analyzed copy number variations in peripheral blood DNA of male participants from the Uppsala Longitudinal Study of Adult Men (aged 70.7–83.6 years). Interestingly, the most frequent shared genetic mutation was LOY, which was found in varying proportions of the blood cells of the individuals, and the proportions became progressively larger as patients aged.

The effect of this mosaic LOY on patient survival was examined in 982 subjects, who were cancer free at the beginning of the study. After a medium time of 8.7 years of follow-up, men with LOY were found to survive on average 5.5 years less than those without LOY and to be at a higher risk of nonhematological cancer-related deaths. No subjects developed hematological cancers. These same results were seen in another 488 adult men from the Prospective Investigation of the Vasculature in Uppsala Seniors study.

The findings suggest a protective function for the Y chromosome in cancer, although how this occurs remains unknown. More detailed studies will be required to analyze the degree of LOY in peripheral blood that predisposes to cancer.