The Impact of Estrogens on Colorectal Polyp Burden in FAP

Bryson Katona MD, PhD, AGAF, CGAF

• Jeffery and Cynthia King Associate

• Professor of Lynch Syndrome Research

• Executive Director, King Center for Lynch Syndrome

• Director, Gastrointestinal Cancer Genetics Program

• Associate Professor of Medicine and Genetics

• Division of Gastroenterology and Hepatology

• University of Pennsylvania Perelman School of Medicine

The Impact of Estrogens on Colorectal Polyp Burden in FAP

In this grant proposal we will investigate whether estrogens can slow polyp growth in FAP.  Estrogens are natural hormones involved in the reproductive and sexual development of women, and there are four major types of estrogen.  Clinically, we have seen that women with polyposis, including FAP, who go through a pregnancy, develop a temporary stagnation or reduction in their polyp burden during pregnancy.  This indicates that it is possible that estrogens, which are increased during pregnancy, may be playing a role in preventing colon polyp growth.  We will test whether each of the four different estrogens is able to reduce the growth of colon and polyp organoids generated from FAP patients.  We will also test whether each of the four estrogens can prevent polyp growth in a mouse model of FAP.  If successful, these proposed experiments will define a novel strategy for chemoprevention in FAP that has potential to be directly translated to improving care, reducing morbidity, and reducing CRC cancer risk for FAP patients.