Cancer Risk, Detection and Interception (CRDI)

hand with earth

Meira Epplein, PhD

Program Co-Leader

Katherine Garman, MD

Program Co-Leader

Program Overview

Research in the Cancer Risk, Detection, and Interception (CRDI) Program spans the continuum of basic, population, clinical, and translational research. Strengths include complementary approaches spanning cancer epidemiology, exposures, and genetics, to promote early intervention and avoid cancer progression. Collectively, CRDI Program Members seek to drive discovery and advances in novel biomarker identification, risk assessment strategies, early detection, and cancer interception.

Globally, the CRDI Program seeks to provide the infrastructure and opportunities to facilitate collaborative research among CRDI members and across the Duke Cancer Institute. Through these collaborations, CRDI members aim to disseminate new knowledge and reduce the burden of cancer both regionally and beyond.

Focus Areas

As a theme threaded throughout the work of its members, CRDI seeks to reduce the cancer burden in the Duke Cancer Institute (DCI) catchment area, as well as addressing cancer health disparities locally, regionally, and globally. Our work can also be categorized into two focus areas, as described below.

Focus Area 1: Risk Identification and Assessment (Leader: Heather Stapleton): Research in this area seeks to improve the prevention of cancer and risk stratification through exposure measurement, discovery of novel risk factors for better risk prediction, identification of high-risk individuals for targeted prevention, and studies of genetic predisposition and cancer initiation.

Focus Area 2: Cancer Detection and Interception (Co-Leaders: Shelley Hwang and Evan Myers): Research in this area seeks to expand cancer detection and interception (primary and secondary) through research into chemoprevention, cancer screening, cutting-edge screening technology, and with a focus in situ/early stage disease.

Leadership Bios

Meira Epplein, PhD, MS, MA, is an epidemiologist specializing in cancer prevention, with a focus on modifiable risk factors, including infection, and health disparities. She has been awarded four grants from the NCI that focus on gaining a greater understanding of the diversity of the bacteria Helicobacter pylori and host response to infection and the association with gastrointestinal cancers. She is committed to supporting transdisciplinary collaboration and training the next generation to further consequential cancer epidemiological research.

Katherine Garman, MD, MHS, is a gastroenterologist and basic/translational scientist focused on the underlying biology associated with carcinogenesis in the upper GI tract. She has NIH funding to study the role of gastrin in esophageal repair and pre-malignant disease as well as the functional significance of genes associated with familial Barrett’s esophagus and esophageal cancer. In partnership with Dr. Epplein, she is co-lead for an NCI-funded P20 project on Helicobacter pylori, gastric intestinal metaplasia and gastric cancer disparities.

Scientific Highlights

This study adapted an ultra-sensitive sequencing platform originally developed to detect mutations arising in bacteria populations to detect de novo mutations in the oncogene KRAS in vivo. Using this assay, it was possible to capture the moment the cancer-causing mutation first occurred in KRAS, helping unravel how cancer first begins, and paving the way for early detection of this disease.

Ancestry-related biology is one of the multi-level contributors to cancer health disparities. Comparative genomic studies of tumor tissues from Black and White patients have revealed novel molecular pathways driving tumor aggressiveness and potential target molecules for precision oncology approaches to cancer therapy.

Currently, the vast majority of women diagnosed with pre-invasive breast cancer (DCIS) undergo surgery. Our findings suggest that DCIS patients without locoregional treatment have a limited risk of progression to invasive breast cancer. This in turn implies that there may be overtreatment, especially among older patients and patients with elevated comorbidities.

In this large genome-wide association study for genetic risk of squamous cell carcinoma of the head and neck (SCCHN) among 7376 cases and 7725 cancer-free controls, the investigators identified a few novel genetic variants in human leukocyte antigen loci for oropharyngeal cancer risk, highlighting the importance of immunologic mechanism against human papilloma virus infection in the disease etiology.

This paper, which uses data from the Utah Population Database, demonstrates the importance of cancer family history information in determining prostate cancer risk in unaffected men. Importantly, men with three or more first degree relatives with prostate cancer or those with two or more first or second degree relatives with early-onset prostate cancer (defined as prostate cancer diagnosed <55 yrs) were at very high risk for early-onset disease. 

Long-term outcomes after colonoscopy screening are relatively uncertain. This study found that baseline screening colonoscopy findings associate with advanced neoplasia within 10 years. To note, individuals with only 1 or 2 small adenomas at baseline have a low risk of advanced neoplasia over 10 years. Alternative surveillance strategies could be considered for these individuals.