Abstract 274: Early-onset colorectal cancer is distinct from traditional colorectal cancer
Authors: Doron Betel, Heather Yeo, Rhonda Yantiss, Xi E. Zheng, Jonathan S. Abelson, Manish A. Shah
Journal: Cancer Research (2017)

Abstract Background &amp; Objective: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer worldwide, responsible for over 700,000 deaths annually. Although CRC rates have declined 3.1%/year annually over the past decade, annual incidence rates of CRC among patients between 20-49 years old have increased by more than 1.4% per year over the same time period and these early-onset CRCs (E-CRC) now comprise 10-18% of newly diagnosed cases. Our hypothesis is that E-CRC represents a distinct subtype of CRC with unique drivers. To examine this, we analyzed national data sources such as the SEER database, the Behavioral Risk Factor Surveillance Survey (BRFSS), and the Cancer Genome Atlas (TCGA) to characterize the epidemiology and genetics differences between early onset CRC (E-CRC) and typical CRC (T-CRC). Methods: The SEER database was analyzed to characterize the clinical and pathological differences between E-CRC patients (20-49 years) and T-CRC group (&amp;gt; 50 years). We compared rates of age-adjusted CRC with known lifestyle risk factors using population data from the BRFSS. Based on differences in clinical presentation and anatomical location we hypothesized that there are underlying molecular differences between E-CRCs and T-CRC that may explain these differences. To investigate this we analyzed the TCGA CRC dataset for genomic markers that can distinguish between E-CRC and T-CRC tumors. Results: E-CRC incidence has risen at an annual rate of 1.4% per year from 2000-2011, whereas T-CRC incidence has declined by 3.1% per year among patients 50 years or older during the same period. Relative to T-CRC, E-CRC rates are significantly more prevalent in the Black population than the White or Hispanic populations. Anatomical location of E-CRC is significantly increased towards the distal colon when compared to T-CRC locations suggesting a distinct etiology. Analysis of risk factors confirmed that U.S counties with high rates of diabetes, obesity and smoking were significantly correlated with higher T-CRC rates. However, no such correlations were observed for E-CRC rates. Analysis of the limited number of E-CRC in the TCGA cohort identified a number of known oncogenes that are suggestive of distinct E-CRC tumorigenesis. Conclusions: Our results suggest that E-CRC appears to be distinct from T-CRC. Young patients with CRC represent a distinct patient group with unique epidemiology and mechanisms of disease development. The increase in left sided colon and rectal cancers is consistent with earlier reports and although the underlying reasons are unknown, they are suggestive of differences in tumor genesis and mutational characteristics. To follow up on this hypothesis we are performing additional genetic and epigenetic characterization of E-CRC and matching T-CRC samples collected at Weill Cornell. Citation Format: Doron Betel, Heather Yeo, Rhonda Yantiss, Xi E. Zheng, Jonathan S. Abelson, Manish A. Shah. Early-onset colorectal cancer is distinct from traditional colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 274. doi:10.1158/1538-7445.AM2017-274