Abstract 2263: Neonatal hormone levels and risk of testicular germ cell tumors (TGCT)

Abstract

Abstract Testicular germ cell tumors (TGCT) are the most commonly occurring cancers in adolescent and young adult males in the U.S. Steroid sex hormones play a central role in the development of the testis. As proposed by the testicular dysgenesis syndrome hypothesis, the origins of TGCT are likely to be in utero or early in life, and to be a manifestation of disturbed prenatal testis development. However, no studies have provided direct, empirical evidence to date. Using an innovative linkage between the California birth records and cancer registry data, we conducted a population-based case-control study of neonatal hormones levels and risk of TGCT diagnosed at 0-19 year of age. We obtained archived neonatal dried blood spot (DBS) specimens from 370 TGCT cases (276 adolescent and young adults [AYA] aged 15-19 yrs at diagnosis; 94 0-4 yrs at diagnosis), and 344 age- and race/ethnicity-matched controls, born between 1982 and 2009. Liquid chromatography with tandem mass spectrometry was used to measure a panel of 17 sex steroids, glucocorticoids, and mineralcorticoids; 12 were present at detectable levels in the newborn DBS samples, including estrone (E1), estradiol (E2), estriol (E3), testosterone (T), dehydroepiandrosterone (DHEA), and androstenedione (A4). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for matching factors and age (in hours) of child at blood spot collection. A4, a precursor for T and E1, was positively associated with TGCT (OR: 1.71, 95% CI: 1.09-2.69). Analyses stratified by age group showed that this association was limited to AYA, and was of stronger magnitude in this group (OR: 2.33, 95% CI: 1.37-3.97). A similar, though weaker, trend was observed for T (ORoverall: 1.37, 95% CI: 0.86-2.19; ORAYA: 1.73. 95% CI: 1.00-3.00). There was no significant association of the other measured hormones with risk. In the first case-control study of TGCT with direct measures of neonatal hormone levels, we found that higher levels of T and A4 were associated with increased risk of TCGT, particularly among males diagnosed at 15-19 years of age. These results oppose the dominant theory in TGCT etiology, that TGCT is related to androgen insufficiency in utero, and provides an important link in the etiologic pathway of this increasingly common cancer. Citation Format: Libby Morimoto, David Zava, Katherine McGlynn, Frank Stanczyk, Joseph Wiemels, Xiaomei Ma, Catherine Metayer. Neonatal hormone levels and risk of testicular germ cell tumors (TGCT) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2263. doi:10.1158/1538-7445.AM2017-2263