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

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岁男性中最常见的恶性肿瘤。过去四十余年间，TGCT的发病率增长了一倍以上，但其病因至今尚未明确。遗传因素与环境暴露（尤其是产前阶段的暴露）均可能在决定TGCT易感性方面发挥重要作用。已知TGCT起源于原始生殖细胞（Primordial germ cells, PGCs）。我们提出假说：影响PGC分化与成熟的基因变异，是决定TGCT易感性的关键因素；基于该假说，我们筛选出三条重点研究通路：其一为男性生殖细胞发育通路，其二为雄激素与雌激素的生物合成及代谢通路，其三为胰岛素样生长因子（IGF）信号通路。参与早期男性生殖细胞发育的蛋白通常仅在PGCs中表达，它们既是TGCT的标志物，且在TGCT中呈过表达状态。雌激素暴露增加（或雄激素暴露相对减少）的标志物……（更多详情请参见dbGaP研究页面。）