Stephanie Schmit, PhD, MPH

Cleveland Clinic Lerner Research Institute

Colorectal Cancer

Pilot Grant

Developing an Epigenetic Age Acceleration Biomarker for Young-Onset Colorectal Cancer Risk Stratification

The Idea: It remains unknown which young adults are at the highest risk for developing young-onset colorectal cancer (YOCRC; <50 years) in the general population. The innovative idea behind this study is to combine what we already know about colorectal cancer risk factors and diseases of aging to discover an easy-to-measure biomarker that would identify a subset of young adults who would benefit from early screening. Certain environmental and lifestyle factors like smoking and obesity have been linked to the development of CRC and also influence epigenetic changes, which are molecular changes that affect how genes work. The cumulative effect of these changes can lead to epigenetic age acceleration (epiAA) – accelerated molecular aging of a person’s tissues. EpiAA captures the difference between chronological age and biological age, thus identifying individuals who are biologically older and at a greater risk for age-related diseases like CRC, than their chronological age indicates. Establishing epiAA as a novel YOCRC biomarker assessed with a blood test would identify high-risk young individuals for colonoscopies.

The Need: New cases of YOCRC have alarmingly increased by over 50% since the mid-1990’s, but the underlying causes are not well understood. Colorectal cancer is a devastating disease at any age, but individuals <50 often have added complications of experiencing this life disruption during their most productive professional years and when raising young families. Findings from this work would not only further our understanding of why YOCRC develops but could also inform personalized risk-based screening recommendations. There is an urgent need to find ways to identify young individuals at higher than average risk for earlier CRC screening. Now is the time to intervene in the curve of this troubling epidemic, informing new interventions through a foundational understanding of the YOCRC drivers.

The Goals: This study is designed to identify a biomarker that reflects the cumulative impact of environmental and lifestyle factors increasing risk for YOCRC and that can be easily measured in blood.

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