Mosaic chromosome Y loss and testicular germ cell tumor risk

J Hum Genet. 2017 Jun;62(6):637-640. doi: 10.1038/jhg.2017.20. Epub 2017 Mar 9.


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.

MeSH terms

  • Adult
  • Chromosome Deletion*
  • Chromosomes, Human, Y / genetics*
  • Cohort Studies
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Infertility, Male / genetics*
  • Infertility, Male / pathology
  • Male
  • Mosaicism
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Risk Factors
  • Testicular Neoplasms / genetics*
  • Testicular Neoplasms / pathology

Supplementary concepts

  • Testicular Germ Cell Tumor