Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer

• Published in: Gut Vol. 70; no. 6; p. 1147
• Main Authors: Chen, Hanyu, Zheng, Xiaobin, Zong, Xiaoyu, Li, Zitong, Li, Na, Hur, Jinhee, Fritz, Cassandra Dl, Chapman, Jr, William, Nickel, Katelin B, Tipping, Andrew, Colditz, Graham A, Giovannucci, Edward L, Olsen, Margaret A, Fields, Ryan C, Cao, Yin
• Format: Journal Article
• Language: English
• Published: England 01-06-2021
• Subjects: Adult; Age of Onset; Case-Control Studies; Colon - pathology; Colonic Neoplasms - epidemiology; Comorbidity; Databases, Factual; Diabetes Mellitus, Type 2 - epidemiology; Female; Humans; Hyperglycemia - epidemiology; Hyperlipidemias - epidemiology; Hypertension - epidemiology; Incidence; Male; Metabolic Syndrome - epidemiology; Middle Aged; Obesity - epidemiology; Rectal Neoplasms - epidemiology; United States - epidemiology; United States; cancer epidemiology; colorectal cancer
• ISSN: 1468-3288
• DOI: 10.1136/gutjnl-2020-321661

Factors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined.
We conducted a nested case-control study among participants aged 18-64 in the IBM MarketScan Commercial Database (2006-2015). Incident CRC was identified using pathologist-coded International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and controls were frequency matched. MetS was defined as presence of ≥3 conditions among obesity, hypertension, hyperlipidaemia and hyperglycaemia/type 2 diabetes, based on ICD-9-CM and use of medications. Multivariable logistic regressions were used to estimate ORs and 95% CIs.
MetS was associated with increased risk of early-onset CRC (n=4673; multivariable adjusted OR 1.25; 95% CI 1.09 to 1.43), similar to CRC diagnosed at age 50-64 (n=14 928; OR 1.21; 95% CI 1.15 to 1.27). Compared with individuals without a metabolic comorbid condition, those with 1, 2 or ≥3 conditions had a 9% (1.09; 95% CI 1.00 to 1.17), 12% (1.12; 95% CI 1.01 to 1.24) and 31% (1.31; 95% CI 1.13 to 1.51) higher risk of early-onset CRC (p
<0.001). No associations were observed for one or two metabolic comorbid conditions and CRC diagnosed at age 50-64. These positive associations were driven by proximal (OR per condition 1.14; 95% CI 1.06 to 1.23) and distal colon cancer (OR 1.09; 95% CI 1.00 to 1.18), but not rectal cancer (OR 1.03; 95% CI 0.97 to 1.09).
Metabolic dysregulation was associated with increased risk of early-onset CRC, driven by proximal and distal colon cancer, thus at least in part contribute to the rising incidence of early-onset CRC.