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. 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. 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. 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. 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.