WHOLE EXOME SEQUENCING FOR NCI (COZEN)

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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.