Association Between Metabolic Syndrome and the Risk of Colorectal Cancer Diagnosed Before Age 50 Years According to Tumor Location

Background & Aims: The increasing prevalence of obesity at younger ages is concurrent with an increased earlier-onset colorectal cancer (CRC) (before age 50 years) incidence, particularly left-sided colon cancer. We investigated whether obesity and metabolic syndrome (MetS) are associated with increased earlier-onset CRC risk according to tumor location. Methods: Our nationwide population-based cohort study enrolled 9,774,081 individuals who underwent health checkups under the Korean National Health Insurance Service from 2009 to 2010, with follow-up until 2019. We collected data on age, sex, lifestyle factors, body mass index (BMI), waist circumference (WC), blood pressure, and laboratory findings. A multivariate Cox proportional hazards regression analysis was performed. Results: A total of 8320 earlier-onset and 57,257 later-onset CRC cases developed during follow-up. MetS was associated with increased earlier-onset CRC (adjusted hazard ratio, 1.20; 95% CI, 1.14–1.27), similar to later-onset CRC (adjusted hazard ratio, 1.19; 95% CI, 1.17–1.21). The adjusted hazard ratios for earlier-onset CRC with 1, 2, 3, 4, and 5 MetS components were 1.07 (95% CI, 1.01–1.13), 1.13 (95% CI, 1.06–1.21), 1.25 (95% CI, 1.16–1.35), 1.27 (95% CI, 1.15–1.41), and 1.50 (95% CI, 1.26–1.79), respectively (P for trend < .0001). We found that higher body mass index and larger waist circumference were significantly associated with increased earlier-onset CRC (P for trend < .0001). These dose–response associations were significant in distal colon and rectal cancers, although not in proximal colon cancers. Conclusions: MetS and obesity are positively associated with CRC before age 50 years with a similar magnitude of association as people diagnosed after age 50 years. Thus, people younger than 50 years with MetS require effective preventive interventions to help reduce CRC risk.