Mosaic chromosome Y loss and testicular germ cell tumor risk

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.