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.

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