Perinatal hormonal biomarkers and risk of testicular germ cell tumors

描述（由申请人提供）：睾丸癌（TC）是青少年和年轻人中最常见的癌症，而在婴儿中罕见。在过去的40年里，美国的TC发病率急剧增加。与非西班牙裔白人相比，西班牙裔白人的发病率和死亡率增长更快，加剧了少数民族的健康差距。TC主要是生殖细胞肿瘤（TGCT），组织学类型（腺瘤与非腺瘤）随年龄而变化。TGCT的危险因素知之甚少。一些条件，如隐睾有助于TGCT的风险，遗传因素最近已被确定。环境因素仍然是TGCT的重要决定因素，发病率的上升就是明证。雌激素和雄激素（也称为类固醇性激素）对睾丸的发育具有核心作用，并且可能在TGCT的病因学中起主导作用，直接或通过暴露于内分泌干扰化学品（如农药中存在的有机氯）而介导。由于其早期发病，TGCT很可能在怀孕期间发展，这是一个男性胎儿暴露于高水平类固醇性激素的时期。TGCT发展的另一个关键窗口可能是从子宫内到子宫外生活的过渡，其特征是母体激素的突然撤回和新生儿自身类固醇性激素和其他调节激素如促性腺激素的出生后激增。评估围产期性激素的潜在作用，包括暴露的时间，在TGCT已被证明是具有挑战性的，主要是由于难以获得诊断前，围产期生物标本。我们提出的探索性研究的目的是提供1988年和2009年（150例年龄为15-19岁和50例年龄为0-4岁）加利福尼亚出生的男性诊断为TGCT的出生激素水平的初步数据，以及200例年龄/种族匹配的对照。我们将使用出生时采集的存档干血斑（DBS）标本，并通过加州儿童癌症记录链接项目（CCRLP）提供给我们。稳健的实验室方法（即，液相色谱-质谱法和免疫测定法）可用于测量类固醇性激素（即，雌酮、雌二醇、雌三醇、睾酮和脱氢表雄酮）和促性腺激素（即，促黄体激素和促卵泡激素）。激素水平将在病例和对照组之间进行比较，并按年龄、组织学和种族组进行比较。我们提出的探索性生物标志物研究将是填补目前非西班牙裔白人和西班牙裔TGCT病因学知识空白的关键一步，以及量化出生时可能涉及其他睾丸疾病（包括不孕症）的性激素水平。

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.