Metabolic Dysregulation Could Contribute to Incidence of Colorectal Serrated Lesions

Metabolic dysregulation could be a contributing factor to the incidence of colorectal cancer (CRC) through the development of colorectal serrated lesions, according to a study published in BMC Cancer. Preventing metabolic syndrome (MetS) could be a key in early diagnosis and treatment of CRC.

Incidence of CRC in patients aged younger than 50 years is increasing in the United States and China. Increased prevalence of MetS may provide a clue to the increasing incidence of CRC. MetS forms metabolic dysregulation, including insulin resistance, hypertension, and central obesity. The retrospective analysis aimed to examine the association between MetS, onset age, and tumorigenesis pathways of CRC.

Gastroenterologist doctor, intestine specialist. Aesthetic handdrawn highlighted illustration of human intestine. Dark grey background, studio photo and collage. | Image credit: mi_viri - stock.adobe.com

The retrospective study took place between January 204 and December 2018 at the Second Hospital, Cheeloo College of Medicine at Shandong University. Patients were included if they were older than 18 years and had curative colorectal endoscopic submucosal dissection/endoscopic mucosal resection (ESD/EMR) for the management of early-stage CRC. Patients with severe systemic diseases, Lynch syndrome, undetailed medical history, coexisting cancers, personal history of inflammatory bowel disease, and hereditary polyposis syndromes were excluded from the study.

All patients had preoperative testing done that included a physical exam, laboratory testing, and a CT scan when scheduled for the colorectal ESD/EMR. Body mass index and blood pressure were collected from all patients. Patients were considered as having MetS if they had at least 3 of obesity, fasting blood glucose of 6.1 mmol/L or more or treatment for diabetes, a systolic/diastolic blood pressure of 130/85 mmHg or higher or treatment for hypertension, and fasting triglycerides of 1.7 mmol/L or higher. Early-stage CRC was defined as having advanced colorectal neoplasia.

There were 120 early-onset CRC and 518 late-onset CRC cases who were included in the study, with the mean (SD) age of diagnosis being 43.5 (4.5) years and 63.2 (8.3) years respectively. Colonoscopy and CT scans were performed 1, 2, 3, and 5 years after patients were first treated. There was no local tumor recurrence in the patients within a 3-year follow-up.

There were 17 (14.2%) patients who had hyperglycemia/type 2 diabetes and 12 (10.0%) patients who had hypertension in the early-onset cohort. The late-onset cohort had higher incidences in both type 2 diabetes (33.8%) and hypertension (39.8%) compared with the early-onset. Patients with MetS were obese (100%) and had hypertriglyceridemia (81.3%) the most among those aged younger than 50 years whereas obesity (81.1%) and hyperglycemia/type 2 diabetes (82.0%) were the most common in those aged 50 years and older with MetS.

The early-onset and late-onset cohorts had 13.3% and 21.4% of patients with MetS respectively. Patients with early-stage CRC aged 50 years and older had MetS that coexisted more frequently compared with patients aged less than 50 years (odds ratio [OR], 1.77; 95% CI, 1.01-3.12) but this was not found in female patients (OR, 0.84; 95% CI, 0.79-0.90). This relationship was stronger in patients who did not smoke (OR, 3.10; 95% CI, 1.29-7.40). A total of 42.5% of patients aged more than 50 years with late-onset CRC had MetS compared with only 13.3% of controls.

Patients without carcinoma with MetS had a higher risk of advanced serrated lesions compared with conventional adenomas (OR, 1.585; 95% CI, 1.02-2.45); the propensity score analysis also found this result. Increasing age made the association between MetS and advanced serrated lesions more statistically significant (OR, 1.78; 95% CI, 1.11-2.85).

There were some limitations to this study. Body mass index was used instead of waist circumstance to diagnose central obesity, which could have misestimated the prevalence of MetS. There was a small sample size in a homogeneous population due to being a single-center analysis. Data on other risk factors like sedentary lifestyle and red or processed meat intake were not available.

The researchers concluded that metabolic dysregulation could contribute to the incidence of serrated lesions in CRC. Preventing MetS could be beneficial, especially in early diagnosis and treatment of patients aged 50 years and older.

Reference

Zhang C, Zhang L, Tian Y, Guan B, Li S. Association between metabolic syndrome and early-stage colorectal cancer. BMC Cancer. 2023;23:1020. doi:10.1186/s12885-023-11537-3