Kathryn Barry

Ph.D., M.P.H.

University of Maryland School of Medicine

Assistant Professor

PLCO (Learn more about this study)

2015-0058

Mar 9, 2015

Epigenetic markers of multiple myeloma risk in peripheral blood DNA

Global DNA hypomethylation and gene-specific hypermethylation have been observed in multiple myeloma. However, it is unknown whether altered DNA methylation levels in peripheral blood DNA are associated with the subsequent risk of developing multiple myeloma. We propose to conduct a prospective study to investigate DNA methylation levels at specific CpG sites throughout the genome in relation to the risk of multiple myeloma using pre-diagnostic blood samples from 200 cases and 400 controls in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We will quantify DNA methylation levels at specific CpG sites using the Illumina Infinium HumanMethylation450 BeadChip. We will use principal components analysis to evaluate the association between global DNA methylation across all evaluated CpG sites and the risk of multiple myeloma. Additionally, we will conduct separate logistic regression models for each CpG site to identify individual sites whose methylation levels are associated with risk. We will also use clustering analysis to identify DNA methylation signatures associated with risk. By evaluating a large number of specific CpG sites in this epigenome-wide study, we anticipate that our findings may provide important insights about mechanisms of myelomagenesis and may also suggest targets for the prevention or treatment of multiple myeloma.