Rami Nassir

1Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 2Center for Computation and Genomic Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA 3Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 4Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA 5The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at...

Abstract Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as leukemogenic point mutations or mosaic chromosomal alterations (mCAs), are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions.

Abstract Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk. We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent.