1571 Background: The etiology and contributors to the rising incidence of early-onset colorectal cancer (CRC diagnosed under age 50), driven largely by distal and rectal cancer, remain largely unknown. Metabolic syndrome is associated with higher risk of CRC diagnosed at older ages; however, its association with early-onset CRC remains unclear. Methods: We conducted a nested case-control study among participants aged 18-50 years with ≥2 years of enrollment and prescription drug coverage in the IBM MarketScan Commercial Databases (2006-2015). Incident CRC cases were identified using ICD-9-CM diagnosis codes. Controls without any cancer were identified using frequency matching on age, sex, geographical region, and duration of insurance enrollment. Metabolic syndrome was defined using either ICD-9-CM diagnosis codes or the presence of at least 3 of the following: obesity, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes. In addition to ICD-9-CM codes, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes were also defined based on regular use of medications. Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 4,673 early-onset CRC and 40,832 controls were included. Metabolic syndrome was associated with increased risk of early-onset CRC (OR: 1.33, 95% CI 1.16-1.52), after adjusting for a range of potential confounders. The number of metabolic comorbid conditions was positively associated with risk of early-onset CRC in a dose-response fashion. Compared to individuals without any conditions, individuals with 1, 2, ≥3 metabolic conditions had a 13% (OR: 1.13, CI 1.04-1.22), 18% (OR: 1.18, CI 1.07-1.31), and 40% (OR: 1.40, CI 1.22-1.61) higher risk of early-onset CRC (Ptrend<0.001), respectively. These associations were driven by proximal (OR for ≥2 vs 0 metabolic comorbid conditions: 1.40, CI 1.15-1.69) and distal colon cancer, OR ≥2 vs 0: 1.25, CI 1.03-1.53), but not rectal cancer (OR≥2 vs 0: 1.07, CI 0.92-1.24). Conclusions: Metabolic syndrome and metabolic comorbid conditions were associated with increased risk of early-onset CRC, largely driven by proximal and distal colon cancer. Metabolic dysregulations may contribute to the rising incidence of early-onset CRC.
Rising incidence of early-onset colorectal cancer in Australia over two decades: Report and review
