Abstract
Studies have suggested mosaic loss of chromosome Y (mLOY) in blood-derived DNA is common in older men. Cohort studies investigating mLOY and mortality have reported contradictory results. Previous work found that a 1.6 Mb deletion of the AZFc region on the Y chromosome (the ‘gr/gr’ deletion) is associated with both male infertility and increased risk of testicular germ cell tumors (TGCT). We investigated whether mosaic loss across the entire Y chromosome was associated with TGCT. We obtained blood- and buccal-derived DNA from two case–control studies: the NCI Familial Testicular Cancer Study (cases=172; controls=163) and the NCI US Servicemen’s Testicular Tumor Environmental and Endocrine Determinants Study (cases=506; controls=611). We used 15 quantitative polymerase chain reactions spanning the Y chromosome to assess mLOY. Multivariate logistic regression models adjusted for study batch effects detected no significant overall relationship between mean chromosome Y target-to-reference (T/R) ratio and TGCT (odds ratio=0.34, 95% confidence interval=0.10–1.17, P=0.09). When restricted to familial TGCT cases, a significantly lower T/R ratio was observed in cases compared with controls (0.993 vs 1.014, P-value=0.01). Our study suggests that mLOY, as measured by 15 probes spanning the Y chromosome, could be associated with familial TGCT, but larger studies are required to confirm this observation.
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This project was funded by the Intramural Research Program of the United States National Cancer Institute, Division of Cancer Epidemiology and Genetics. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government.
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Machiela, M., Dagnall, C., Pathak, A. et al. Mosaic chromosome Y loss and testicular germ cell tumor risk. J Hum Genet 62, 637–640 (2017). https://doi.org/10.1038/jhg.2017.20
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DOI: https://doi.org/10.1038/jhg.2017.20
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