Inherited Genetic Variation and Predisposition to Testicular Germ Cell Tumor. Homo sapiens

Testicular germ cell tumors (TGCT) are the most common cancer in men ages 20-40. The incidence of TGCT has more than doubled over the past forty years, without clear etiology. Both genetic effects and environmental exposures, specifically during the pre-natal period, are likely to play an important role in determining TGCT susceptibility. TGCT is known to develop from primordial germ cells (PGCs). We hypothesize that variation in genes that impact upon the differentiation and maturation of PGCs will be important determinants of TGCT susceptibility and based on this hypothesis have selected three important pathways for study, i) male germ cell development, ii) androgen and estrogen biosynthesis and metabolism, and iii) IGF signaling. The proteins involved in early male germ cell development, normally only expressed in PGCs, are markers of and are overexpressed in TGCT. Markers of increased exposure to estrogen (or relatively decreased exposure to androgen... (for more see dbGaP study page.)

睾丸生殖细胞肿瘤（Testicular Germ Cell Tumors, TGCT）是20至40岁男性群体中最常见的恶性肿瘤。过去四十余年间，其发病率已翻倍有余，但具体病因仍未明确。遗传因素与环境暴露（尤其是产前阶段的暴露）可能在TGCT易感性的决定过程中发挥关键作用。已知TGCT起源于原始生殖细胞（Primordial Germ Cells, PGCs）。本研究提出假说：影响原始生殖细胞分化与成熟的基因变异，是决定TGCT易感性的核心因素；基于该假说，我们选定了三条重要研究通路：① 雄性生殖细胞发育通路，② 雄激素与雌激素的生物合成及代谢通路，③ 胰岛素样生长因子（Insulin-like Growth Factor, IGF）信号通路。参与早期雄性生殖细胞发育的蛋白质通常仅在原始生殖细胞中表达，它们既是TGCT的特异性标志物，且在TGCT组织中呈高表达状态。雌激素暴露升高（或雄激素暴露相对降低）的相关标志物……（更多详情请参见dbGaP研究页面）