Genetic Predictors of Prostate Cancer Survival

摘要 本申请是为了响应特别利益通知（NOSI）而提交的，该通知被确定为 NOT-CA-21-049。尽管大多数被诊断患有前列腺癌的男性不会死于这种疾病， 前列腺癌仍然是美国男性癌症死亡的第二大原因。而 筛查前列腺癌可以减少疾病的死亡，这是以不必要的 活组织检查显示没有癌症的证据，治疗其他惰性癌症， 不必要的不良事件。因此，对于用于前列腺疾病的改进的筛查工具存在未满足的需求。 癌这种需求在非洲裔美国人中尤其重要，因为非洲裔美国人是 两者都更有可能被诊断出患有前列腺癌，并且如果被诊断出患有前列腺癌，则更有可能死于该疾病。然而，在这方面， 迄今为止，大多数关于前列腺癌的遗传学研究都是在欧洲血统的个体中进行的。 为了满足这一需求，我们正在进行一项由国家癌症研究所资助的研究，“前列腺癌的遗传预测因子 生存”，其目标是确定与前列腺患者生存时间相关的遗传变异， 癌这将通过检测两种插补基因表达水平来实现，这两种基因表达水平来自常见的 变异，以及编码基因的致病性变化，源自罕见的编码变异，具有存活性。在 最初的赠款，我们提出了验证我们的研究结果使用几个队列，包括一系列的300激进 我们收集了来自达勒姆VA医院的非裔美国患者的乳房切除术患者。 在这里，我们建议通过检索样本和提取临床注释将样本量增加一倍 这一组中的另外300名非裔美国人。然后，这些样本将使用 CIDR的资源。随着它们在dbGaP中的沉积，这种遗传数据将增加功率， 我们对前列腺癌生存的遗传学研究的多样性，对其他研究基因组学的人有帮助。 对非裔美国人疾病的影响，既因为他们的前列腺癌数据， 用于其他研究。

Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-21-049. Even though most men diagnosed with prostate cancer will not die of the disease, prostate cancer is still the second leading cause of cancer death among men in the United States. While screening for prostate cancer reduces death from disease, this comes at the price of both unnecessary biopsies that reveal no evidence of cancer and treatment of otherwise indolent cancer resulting in unnecessary adverse events. Therefore, there is an unmet need for improved screening tools for prostate cancer. This need is especially important in the African-American population, as African-American men are both more likely to be diagnosed with prostate cancer and to die from the disease if diagnosed. However, to date, most genetic studies on prostate cancer have been conducted in individuals of European ancestry. To address this need, we are conducting an NCI-funded study, “Genetic Predictors of Prostate Cancer Survival”, whose goal is to identify genetic variants associated with survival time in men with prostate cancer. This will be achieved both by testing both imputed gene expression levels, derived from common variants, and pathogenic changes in coding genes, derived from rare coding variants, with survival. In the initial grant, we proposed to validate our findings using several cohorts, including a series of 300 radical prostatectomy patients from African-American patients from the Durham VA hospital we have collected. Here, we are proposing to double the sample size by retrieving samples and extracting clinical annotation for an additional 300 African-American men from this cohort. These samples will then be genotyped using the resources of CIDR. With their deposition in dbGaP, this genetic data will both increase the power and diversity of our studies of the genetics of prostate cancer survival and be of use to others studying genomic influences on disease in African-Americans, both for their data on prostate cancer and as a reference panel for other studies.