Metabolic Dysregulation Is Linked to Early-Onset Colorectal Cancer

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Investigators conducted a nested case-control study to evaluate the clinical link between metabolic syndrome and early-onset colorectal cancer (CRC). Although the factors that led to metabolic dysregulation are associated with increased risk for early-onset CRC, this association has remained largely unexamined.

Metabolic dysregulation was found to be a major risk factor for early-onset colorectal cancer (CRC), increasing the propensity for early disease development by 25%, according to study data published in Gut. This trend was specifically driven by increased rates of proximal and distal colon cancer in patients with metabolic syndrome (MetS).

Investigators conducted a nested case-control study using healthcare claims data extracted from the IBM MarketScan Commercial Database to evaluate the association between MetS and early-onset CRC. Adults aged 18 to 64 years who were diagnosed with incident CRC between 2006 and 2015 were eligible for inclusion.

Early-onset CRC was defined as disease diagnosed in individuals younger than 50 years. Patients with CRC were frequency matched to controls without CRC by age group, sex, duration of insurance enrollment, and region of residence. MetS was identified using either the International Classification of Diseases, Ninth Revision, Clinical Modification codes or the presence of 3 of the following 4 conditions: obesity; hypertension; hyperlipidemia; and hyperglycemia/type 2 diabetes. Multivariable logistic regression was used to assess the prevalence rates of metabolic dysregulation in patients with and without early-onset CRC. Analyses were adjusted for matching factors and other relevant covariates.

The study cohort comprised 4673 patients with early-onset CRC and 40,832 frequency-matched controls. In adjusted regression models, MetS was associated with a substantially increased risk for early-onset CRC (odds ratio [OR], 1.25; 95% CI, 1.09-1.43). The number of metabolic comorbid conditions was positively associated with risk of early-onset CRC in a dose-dependent manner. Compared with individuals without any metabolic comorbidities, those with 1, 2, or ≥3 conditions had a 9% (OR, 1.09; 95% CI, 1.00-1.17), 12% (OR, 1.12; 95% CI, 1.01-1.24), and 31% (OR, 1.31; 95% CI, 1.13-1.51) increased risk for early-onset CRC (P <.001). Further, each additional metabolic comorbid condition was associated with a 10% increased risk for overall colon cancer (OR, 1.10; 95% CI, 1.05-1.15), a 14% higher risk for proximal colon cancer (OR, 1.14; 95% CI, 1.06-1.23), a 9% elevated risk for distal colon cancer (OR, 1.09; 95% CI, 1.00-1.18), and an 8% increased risk for unspecified colon cancer (OR, 1.08; 95% CI, 1.01-1.15).

This trend persisted in subgroup analyses defined by sex, urbanicity, and geographic region. When analyses were stratified by cancer site, MetS was significantly associated with early-onset colon cancer (OR, 1.38; 95% CI, 1.18-1.62) but not rectal cancer (OR, 1.04; 95% CI, 0.83-1.32). In particular, MetS was strongly associated with increased risk for proximal and distal cancer.

Results from the study suggest that MetS and metabolic conditions may significantly increase the risk for early-onset CRC. Notably, MetS and comorbid metabolic conditions remained significant when the investigators adjusted for potential confounding factors and indicators for healthcare utilization. The authors therefore hypothesized that “metabolic dysregulation may at least in part contribute to the rising incidence of early-onset CRC” and posited that “prevention of MetS among younger adults should be further prioritized in the context of cancer prevention.”

The study’s use of claims data presented certain limitations. For example, laboratory values were not available, nor was information on lifestyle factors. More detailed patient information is needed to better parse out the influence of MetS on early-onset CRC risk, according to the authors. 

“MetS may be useful in tailoring clinical algorithms to assess risk of early-onset CRC among younger adults. [However,] prevention of MetS is likely critical for CRC prevention at all ages,” the investigators concluded.


Chen H, Zheng X, Zong X, et al. Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer. Gut. Published online October 9, 2020. doi:10.1136/gutjnl-2020-321661