WHOLE EXOME SEQUENCING FOR NCI (COZEN)

NCI 全外显子组测序 (COZEN)

• 批准号: 10949127
• 负责人: Kimberly F Doheny
• 金额: $ 63.46万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-14 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10949127
• 关键词: WHOLE; EXOME; SEQUENCING; NCI; COZEN

Multiple myeloma (MM) is a fatal cancer of plasma cells that is 2-3 times more common among Blacks and 3-4 times less common among Asians compared to whites for unknown reasons, comprising one of the major cancer disparities. (Monoclonal gammopathy of undetermined significance (MGUS) is a benign clone of plasma cells that is a necessary precursor of MM, which mirrors the same racial disparity as MM. In an ongoing study we hypothesize that racial differences in plasma cell growth/angiogenic factors, chronic antigenic stimulation due to previous infection and bacterial translocation as well as lifestyle factors can explain this disparity. In addition, we hypothesize that genetic variation will also contribute to the MGUS and MM disparity. Thus, further exploration of genetic risk factors for the MGUS/MM risk disparity is warranted and fills a knowledge gap. We have 1,813 DNA samples from our MM GWAS conducted in Blacks and propose whole exome sequencing (WES) to better capture genetic variation that could be contributing to MM risk in this high-risk population. We will leverage existing WES from CIDR for 3,350 Black prostate cancer controls as a comparison group. With our collaboration of the 4 most racially and ethnically diverse cancer epidemiology cohorts and samples from the only GWAS conducted for MM among Blacks, we are uniquely positioned to be able to further identify genetic causes of the MGUS and MM risk disparity. Better understanding of the causes of the risk disparity for MM and MGUS could lead to prevention of progression (of MGUS to MM) or earlier treatment, known to have a positive effect on survival. Primary prevention (prevention of MGUS) is also possible with better understanding of susceptibility pathways. Prevention could be tailored to specific racial/ethnic groups.

多发性骨髓瘤（MM）是血浆细胞的致命癌，与白人相比，由于未知原因，在黑人中的常见2-3倍，在亚洲人中的普遍性少于3-4倍，其中包括主要的癌症差异之一。 （不确定显着性（MGU）的单克隆性伽马病是浆细胞的良性克隆，是MM的必要前体，它反映了与MM相同的种族差异。在一项正在进行的研究中，我们假设血浆细胞生长/血管生长因子的种族差异，慢性抗原因素，慢性抗原因素，慢性抗原因素 由于先前的感染和细菌易位以及生活方式因素而引起的刺激可以解释这种差异。此外，我们假设遗传变异也将导致MGU和MM差异。 因此，有必要进一步探索MGU/MM风险差异的遗传风险因素，并填补知识差距。 我们有1,813个DNA样品 我们的MM GWAS以黑色进行，并提出了整个外显子组测序（WES），以更好地捕获这种高危人群中可能导致MM风险的遗传变异。我们将利用CIDR的现有WES作为比较组3,350个黑色前列腺癌控制。通过我们在种族和种族上最多样化的四种癌症流行病学人群和来自黑人中MM唯一的GWAS的样本的合作，我们唯一地定位了能够进一步识别的遗传原因 MGU和MM风险差异。更好地了解MM和MGU的风险差异的原因可能导致预防（MGUS至MM）或更早治疗的进展，这对生存具有积极作用。一级预防（预防MGU）也可以更好地理解易感途径。预防可以针对特定的种族/族裔量身定制。