Ovarian Cancer and Gonadotropin Signaling

描述（由申请人提供）：卵巢癌是妇科肿瘤死亡的主要原因，也是女性癌症死亡的第四大常见原因。2005年，据估计，在美国将诊断出22，220例新病例，16，210名妇女将死于该疾病（美国癌症协会事实和数字，2005）。侵袭性上皮性卵巢癌（卵巢癌）的高致死率主要是由于其通常被诊断为晚期，此时治愈性治疗无效。早期诊断的努力因筛查方法的不良表现而受挫。因此，非常需要增加有关卵巢癌的风险因素和潜在原因的信息。卵巢癌的原因尚不清楚，但被认为是多因素的，激素，遗传和环境因素起作用。最强有力的假设侧重于排卵和/或生殖激素，并基于一致的流行病学证据和确证的体外实验结果。此外，遗传因素也起作用，卵巢癌患者亲属的风险增加。目前，这些观察结果为卵巢癌生物学提供了最有希望的线索。一个有吸引力的假设是，遗传风险的一个重要部分可能是由于影响生殖内分泌的基因变异。我们正在使用两项已完成的病例对照研究的样本，检测促性腺激素信号转导相关基因变异与卵巢癌风险之间的关联。我们在此申请资金，通过对最近完成的第三项卵巢癌研究中的其他病例和对照进行基因分型，扩大该数据集的样本量，目的是（1）提供促性腺激素信号传导相关基因变异与卵巢癌风险之间相关性的可靠结果，（2）通过组织学和环境暴露（如口服避孕药的使用，产次，和绝经期激素治疗;（3）进行促性腺激素信号通路分析，以了解这些基因共同影响卵巢癌风险的复杂方式。

DESCRIPTION (provided by applicant): Ovarian cancer is the leading cause of death from gynecological tumors and the fourth most frequent cause of death from cancer in women. In 2005, it is estimated that 22,220 new cases will be diagnosed and 16,210 women will die of the disease in the U.S. (American Cancer Society Facts and Figures, 2005). The high lethality of invasive epithelial ovarian cancer (ovarian cancer) is primarily due to the advanced stage at which it is typically diagnosed, when curative therapy is ineffective. Efforts at early diagnosis have been frustrated by the poor performance of screening methods. Thus, there is tremendous need for increased information about the risk factors for and underlying causes of ovarian cancer. The cause of ovarian cancer is unknown, but is thought to be multifactorial, with hormonal, genetic, and environmental factors playing a role. The most strongly established hypothesis focuses on ovulation and/or reproductive hormones and is based upon consistent epidemiological evidence and corroborative in vitro experimental results. In addition, genetic factors play a role, with increased risk in relatives of ovarian cancer patients. At present, these observations offer the most promising clues to ovarian cancer biology. An attractive hypothesis is that a significant part of the genetic risk may be due to variation in genes that influence reproductive endocrinology. We are testing the association between variation in genes involved in gonadotropin signaling and risk of ovarian cancer using samples from two completed case-controls studies. We are requesting funds here to expand the sample size of this data set by genotyping additional cases and controls from a third recently completed ovarian cancer study with the aims of (1) providing robust results of the association between variation in genes involved in gonadotropin signaling and risk of ovarian cancer, (2) exploring the relationship between variation in genes involved in gonadotropin signaling and risk of ovarian cancer by histology and environmental exposures such as oral contraceptive use, parity, and menopausal hormone therapy and (3) conducing a 'gonadotropin signaling pathway analysis' to understand the complex manner in which these gene jointly influence ovarian cancer risk.