WHOLE EXOME SEQUENCING FOR NCI (COZEN)

多发性骨髓瘤(MM)是一种致命的浆细胞癌，由于不明原因，黑人的发病率是黑人的2-3倍，亚洲人的发病率比白人低3-4倍，这是主要的癌症差异之一。(未确定意义的单克隆性伽马病(MGUS)是浆细胞的良性克隆，是MM的必要前驱，反映了与MM相同的种族差异。在一项正在进行的研究中，我们假设浆细胞生长/血管生成因子、慢性抗原性的种族差异 既往感染和细菌易位引起的刺激以及生活方式因素可以解释这种差异。此外，我们假设遗传变异也会导致MGUS和MM的差异。 因此，进一步探索MGUS/MM风险差异的遗传风险因素是必要的，并填补了一个知识空白。我们有1813个DNA样本来自 我们的多发性骨髓瘤是在黑人中进行的，并提出了完整的外显子组测序(WES)，以更好地捕捉可能导致这一高危人群多发性骨髓瘤风险的遗传变异。我们将利用CIDR现有的WES作为对照组，用于3,350名黑人前列腺癌对照。在我们与4个种族和民族最多样化的癌症流行病学队列和来自唯一为黑人MM进行的GWA样本的合作下，我们处于独特的地位，能够进一步确定MM的遗传原因。 MGUS和MM的风险差距。更好地了解MM和MGUS风险差异的原因可能导致(MGUS向MM)进展的预防或早期治疗，已知这对生存有积极影响。如果更好地了解易感途径，初级预防(预防MGUS)也是可能的。可以针对特定的种族/民族群体进行预防。

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.