Cancer Epidemiol Biomarkers Prev

Abstract

BackgroundTesticular germ cell tumor (TGCT) incidence has increased over the last 40 years in the United States. In contrast to TGCT among infants, it is hypothesized that TGCT in adolescents and young men is the result of sex steroid hormone imbalance during early fetal development. However, little is known about the neonatal period when abrupt hormonal changes occur, and direct supporting evidence is scarce due to the difficulties in obtaining pre-diagnostic specimens.MethodsWe conducted a population-based case-control study examining hormone levels at birth among 91 infants (0\u20134 years) and 276 adolescents (15\u201319 years) diagnosed with TGCT, and 344 matched controls. Estrogen and androgen levels were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from archived newborn dried blood spots. Logistic regression models were used to estimate the association between each hormone level and TGCT risk.ResultsHigher levels of androstenedione were associated with increased TGCT risk among adolescents (OR: 2.33, 95% CI: 1.37\u20133.97 for highest vs. lowest quartile; p-trend=0.003) but not among infants (OR: 0.70, 95% CI: 0.28\u20131.77). A similar pattern was observed for testosterone (OR: 1.73, 95% CI: 1.00\u20133.00,) although the trend was not significant (p-trend=0.12). Associations were stronger among non-Hispanic white subjects, relative to Hispanics. There was no difference by tumor histologic subtype. Estriol (the only detectable estrogen) was not associated with TGCT risk in either age group.ConclusionsHigher levels of neonatal androgens were associated with increased risk of TGCT among adolescents, suggesting that early life hormone levels are related to the later development of TGCT.HHSN261201000140C/CA/NCI NIH HHS/United StatesHHSN261201000035C/CA/NCI NIH HHS/United StatesUL1 TR001863/TR/NCATS NIH HHS/United StatesHHSN261201000035I/CA/NCI NIH HHS/United StatesHHSN261201000034C/CA/NCI NIH HHS/United StatesU58 DP003862/DP/NCCDPHP CDC HHS/United StatesR21 CA185725/CA/NCI NIH HHS/United States2019-04-01T00:00:00Z29475970PMC58847186095vault:2775