Introduction: Early-onset colorectal cancer (CRC), as defined by CRC diagnosed before age 50, has been increasing in the past 2 decades, with unidentified reasons. Type 2 diabetes increases risk of CRC with average age of onset, however, epidemiological data linking type 2 diabetes and risk of early-onset CRC is thus far limited.

Methods: To examine the association between type 2 diabetes and risk of early-onset CRC, we conducted a nested case-control study of early-onset CRC among participants aged 18-50 years with at least 2 years and 3 months of continuous enrollment in the IBM® MarketScan® Research Databases (2006-2015), the largest database that covers healthcare claims from over 150 million privately insured adults in the US. Incident CRC cases were identified using ICD-9-CM diagnosis codes on pathologists' claims. For cases, the index dates were set at the first pathologist date. Controls without CRC were identified using 1:8 frequency matching on age, sex, and geographical region, duration of insurance enrollment, and Rx coverage. Type 2 diabetes within 2 years of the index dates were identified through the ICD-9-CM and confirmed by Klabunde algorithm. Multivariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).

Results: A total of 5986 early-onset CRC cases were identified. Type 2 diabetes was significantly associated with an increased risk of early-onset CRC (prevalence in cases/controls: 7.2% vs 4.3%; OR: 1.40, 95% CI 1.24-1.56), after adjusting for the matching factors, health care utilization, Charlson Comorbidity Index, obesity, inflammatory bowel disease (IBD), colonoscopy and fecal occult blood test (FOBT), and family history of gastrointestinal neoplasm. Notably, the association between type 2 diabetes and early onset-CRC was similar for colon (OR: 1.44, 95% CI 1.25-1.64) and rectal cancer (OR: 1.30, 95% CI 1.18-1.56) (Pheterogeneity = 0.41). These associations remain similar while we restricted the analyses to individuals without IBD, endoscopy/FOBT, or early symptoms, respectively. In addition, the findings were also similar for women and men, as well as CRC diagnosed before and after age 45.

Conclusions: Type 2 diabetes was associated with increased risk of early-onset CRC with similar strength of associations for colon and rectal cancer.

Citation Format: Zitong Li, Xiaobin Zheng, Katelin B. Nickel, Hanyu Chen, Andrew Tipping, Long H. Nguyen, Andrew T. Chan, Ryan C. Fields, Nicholas O. Davidson, Edward Giovannucci, Margaret A. Olsen, Peter T. Campbell, Graham A. Colditz, Yin Cao. Diabetes and risk of early-onset colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2351.