Biomarkers of Ovarian Cancer Risk: A Prospective Study

描述（由申请人提供）： 卵巢癌是女性生殖器第二常见的恶性肿瘤 道和最常见的死因妇科癌症在 美国的目前，只有20%的卵巢癌患者 在局部阶段诊断，大多数患者在 以预后差为特征的晚期。最有前途的 改进筛查和确定有可能感染艾滋病毒的妇女的方法 卵巢癌可利用血清生物学标志物。第一 为此目的提出的生物标志物是抗原决定簇 CA125然而，CA 125作为一个单一的测量检测只有约一半的 在I期卵巢癌中，它可能在良性妇科肿瘤中升高， 条件因此，CA 125在一个单一的场合，作为一个单独的 标记物，不具有足够的灵敏度和特异性作为筛选 test. 我们假设，涉及使用多种生物标志物的新策略 可以大大提高筛选方法的灵敏度和特异性， 治疗卵巢癌。在这项申请中，我们建议集中于一个 CA 125与新的有前途的生物标志物的组合， 卵巢癌发生的途径，其中包括：溶血磷脂酸 (LPA)，一种参与有丝分裂和增殖的磷脂生长因子 和可溶性Fas（sFas），一种卵巢上皮细胞受损的标志物， 细胞凋亡，这可能导致卵巢间质的形成和持续存在 包涵体囊肿和随后的癌变。 我们建议评估一组血清生物标志物的潜在价值 CA 125、LPA、sFAS检测早期卵巢癌的病例对照研究 一项嵌套在三个参与前瞻性队列中的研究：纽约 大学妇女健康研究;瑞典北方健康和疾病研究; 和挪威奥斯陆大学医院的Janus血清库。

DESCRIPTION (provided by applicant): Ovarian cancer is the second most common malignancy of the female genital tract and the most common cause of death from gynecological cancer in the United States. At present, only 20 percent of ovarian cancer patients are diagnosed at localized stage and the majority of patients are diagnosed at advanced stages characterized by poor prognosis. One of the most promising approaches to improved screening and identification of women at risk of ovarian cancer could be the use of serum biological markers. The first biomarker that was proposed for this purpose was an antigenic determinant CA125. However, CA125 as a single measurement detects only about half of the ovarian cancers at Stage I and it may be elevated in benign gynecological conditions. Consequently, CA125 used on a single occasion, as a solitary marker, does not have an adequate sensitivity and specificity as a screening test. We hypothesize that the new strategies involving use of multiple biomarkers can substantially improve the sensitivity and specificity of screening methods for ovarian cancer. With this application, we propose to concentrate on a combination of CA125 with novel promising biomarkers affecting different pathways of ovarian carcinogenesis, which include: lysophosphatidic acid (LPA), a phospholipid growth factor involved in mitogenesis and proliferation of ovarian epithelial cells; and soluble Fas (sFas), a marker of impaired apoptosis, which may lead to formation and persistence of ovarian stroma inclusion cysts and subsequent carcinogenesis. We propose to assess a potential value of the panel of serum biomarkers (CA125, LPA, sFAS) for early detection of ovarian cancer in a case-control study nested within three participating prospective cohorts: the New York University Women's Health Study; the Northern Sweden Health and Disease Study; and the Janus Serum Bank at Oslo University Hospital, Norway.