Perinatal hormonal biomarkers and risk of testicular germ cell tumors

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DESCRIPTION (provided by applicant): Testicular cancers (TC) are the most common cancers in adolescents and young adults, while rare in infants. TC incidence increased dramatically in the US the past 40 years. Compared to non-Hispanic Whites, the incidence and mortality rates are increasing more rapidly in Hispanics, worsening minority health disparities. TC is mostly germ cell tumors (TGCT) and the histologic types (seminomas vs. nonseminomas) vary with age. The risk factors of TGCT are poorly understood. A few conditions such as cryptorchidism contribute to TGCT risk, and genetic factors have been recently identified. Environmental factors remain important determinants of TGCT, as evidenced by the raise in incidence rates. Estrogens and androgens (also called steroid sex hormones) have a central role on the development of the testis, and may play a dominant role in the etiology of TGCT, either directly or via mediation by exposure to endocrine disrupting chemicals such as organochlorines present in pesticides. Because of its early onset, TGCT are likely to develop during pregnancy, a period when the male fetus is exposed to high levels of steroid sex hormones. Another critical window for the development of TGCT may be the transition from intra-uterine to extra-uterine life, which is marked by an abrupt withdrawal of maternal hormones and a postnatal surge of the newborns' own steroid sex hormones and other regulatory hormones such as gonadotropins. Assessing the potential role of perinatal sex hormones, including the timing of exposure, in TGCT has proven challenging, mainly due to difficulties in obtaining pre-diagnosis, perinatal biospecimens. The objective of our proposed exploratory study is to provide preliminary data on birth hormone levels in California-born males diagnosed with TGCT from 1988 and 2009 (150 cases aged 15-19 years and 50 cases aged 0-4 years) and 200 age/ethnicity-matched controls. We will use archived dried bloodspot (DBS) specimens collected at birth and available to us through the California Childhood Cancer Record Linkage Project (CCRLP). Robust laboratory methods (i.e., liquid chromatography- mass spectrometry and immunoassays) are available to measure steroid sex hormones (i.e., estrone, estradiol, estriol, testosterone, and dehydroepiandrosterone) and gonadotropins (i.e., luteinizing hormone and follicle-stimulating hormone) in DBS specimens. Hormone levels will be compared between cases and controls overall, and by age, histologic, and ethnic group. Our proposed exploratory biomarker study will be a key step towards filling gaps in the current knowledge of TGCT etiology in non-Hispanic Whites and Hispanics, as well as quantifying sex hormone levels at birth that may be involved in other testicular conditions including infertility.