Gastrointestinal (GI) cancers are a major cause of mortality and morbidity in the U.S. and their treatment
uses a substantial proportion of healthcare resources. Of the GI cancers, colorectal cancer (CRC) and
esophageal cancer (EAC) account for a majority of the cancer related deaths, and both are preventable by
screening and surveillance. The current screening tests are suboptimal and have variable success.
A major goal of CRC screening tests is to identify advanced tubular and serrated adenomas, which are
high-risk for becoming CRC, as well as early stage CRC. The risk for CRC is variable with some people being
at high risk because of family histories of CRC, hereditary cancer syndromes, or a personal history of adenomas.
High risk people are placed on aggressive colonoscopy based surveillance programs and low-risk people are
placed on minimal surveillance programs. Unfortunately, our current system for identifying high and low CRC
risk is suboptimal resulting in under and over surveillance and preventable interval CRCs. Better risk markers
for CRC to are needed to prevent interval CRCs and improve the overall effectiveness of CRC screening.
Analogous to CRC, EAC arises from a precancerous condition of the esophagus called Barretts
esophagus (BE), which is a specialized intestinal metaplasia of the esophagus and the highest risk factor for
EAC. It is present in 5% of the US population. BE progresses to EAC through successive histologic steps of
low grade dysplasia (LGD), high grade dysplasia (HGD) and then EAC. Screening and surveillance for BE is
recommended using serial upper endoscopy, which is controversial in its effectiveness for preventing deaths
from EAC. This is in part because, as with CRC, BE patients have variable risk of EAC and are placed on high-
risk and low-risk screening programs. However, the current system for assigning risk is not accurate and the
current screening test is expensive. More cost effective and accurate EAC and HGD screening/surveillance
assays and accurate BE risk biomarkers are needed.
We propose to develop an EDRN BCC that is integrated into the EDRN consortium and, through
collaborations within and outside the EDRN, will develop effective GI cancer screening biomarkers. We propose
to identify, validate, and develop accurate CLIA compliant risk biomarkers for CRC and for EAC in order to
prevent EAC and CRC missed under current screening protocols. Moreover, the accurate risk stratification of
patients for CRC and EAC will reduce the financial impact of current CRC and EAC prevention programs. We
also propose to identify and validate accurate CLIA compliant early detection markers for HGD and early stage
EAC that can be used in an inexpensive, non-endoscopic surveillance test.