Perinatal hormonal biomarkers and risk of testicular germ cell tumors

围产期激素生物标志物和睾丸生殖细胞肿瘤的风险

• 批准号: 8926913
• 负责人: Catherine Metayer
• 金额: $ 17.07万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-12 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8926913
• 关键词: Adolescent and Young Adult; Adult; Affect; Age; Androgens; Animal Model; Apoptosis; Archives; Biological Assay; Biological Markers; Birth; Blood; Blood specimen; California; Cell Differentiation process; Cell Proliferation; Cell division; Chlorinated Hydrocarbons; Cryptorchidism; Data; Development; Diagnosis; Endocrine Disruptors; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Estradiol; Estriol; Estrogens; Ethnic Origin; Ethnic group; Etiology; Exposure to; Female; Fetus; Follicle Stimulating Hormone; Germ cell tumor; Goals; Gonadal Steroid Hormones; Gonadotropins; Health; Hispanics; Histologic; Histology; Hormonal; Hormone use; Hormones; Hypospadias; Immunoassay; Incidence; Infant; Infertility; Knowledge; Laboratories; Life; Luteinizing Hormone; Malignant Childhood Neoplasm; Malignant Neoplasms; Malignant neoplasm of testis; Measurement; Measures; Mediation; Medical; Methods; Neonatal; Newborn Infant; Not Hispanic or Latino; Obesity; Organ; Pathway interactions; Patient Self-Report; Perinatal; Perinatal Exposure; Pesticides; Pilot Projects; Placenta; Play; Population Heterogeneity; Pregnancy; Property; Puberty; Race; Reproductive History; Risk; Risk Factors; Role; Seminoma; Series; Serum; Specimen; Spottings; Surrogate Markers; Teratoma; Testicular Diseases; Testicular Germ Cell Tumor; Testis; Testosterone; Time; Whole Blood; Withdrawal; Yolk Sac Tumor; aged; base; carcinogenesis; case control; dehydroepiandrosterone; early onset; fetal; genetic risk factor; genetic variant; health disparity; hormone regulation; hypothalamic pituitary gonadal axis; liquid chromatography mass spectrometry; male; minority health; mortality; peptide hormone; postnatal; reproductive; response; steroid hormone

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.

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，而在婴儿中很少见。在过去的40年中，美国的发病率急剧增加。与非西班牙裔白人相比，西班牙裔的发病率和死亡率越来越快，少数族裔健康差异恶化。 TC主要是生殖细胞肿瘤（TGCT），而组织学类型（Seminomas vs.非emin瘤）随着年龄的增长而变化。 TGCT的危险因素知之甚少。诸如隐齿术等一些条件有助于TGCT风险，并且最近已经确定了遗传因素。环境因素仍然是TGCT的重要决定因素，这可以提高发病率。雌激素和雄激素（也称为类固醇性激素）在睾丸的发展中起着核心作用，并且可能直接或通过暴露于在农药中存在的内分泌化学物质（例如有机氯）来直接或通过介导，在TGCT的病因中起主要作用。由于其早期发作，TGCT可能会在怀孕期间发展，这是雄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户外细胞内到外矿的过渡，这标志着孕产妇激素的突然戒断以及新生儿自身的类固醇性激素和其他调节激素的产后激增，例如雌雄同体。在TGCT中评估围产期性激素的潜在作用，包括暴露时间，这是具有挑战性的，这主要是由于难以获得诊断前诊断，围产期生物测量。我们拟议的探索性研究的目的是提供有关1988年和2009年诊断为TGCT的出生雄性孕妇的初步数据（150例15-19岁的病例，50例0-4岁的0-4岁病例）和200年龄/种族匹配的对照。我们将使用出生时收集的存档干血点（DBS）标本，并通过加利福尼亚儿童癌症记录连锁项目（CCRLP）提供。强大的实验室方法（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（即雌激素，雌二醇，雌二醇，雌二醇，睾丸激素和脱氢表型）和促性腺激素（即，柠檬粉激素和纤毛蛋白酶），以刺激蛋白质）。总体上以及年龄，组织学和种族群体之间将比较激素水平。我们提出的探索性生物标志物研究将是填补非西班牙裔白人和西班牙裔TGCT病因学知识的差距的关键步骤，并在包括不育在内的其他睾丸条件下可能涉及的出生时量化性激素水平。