Cancer Res Treat.  2024 Jan;56(1):238-246. 10.4143/crt.2023.539.

Association between Metabolically Healthy Status and Risk of Gastrointestinal Cancer

• Cui H
• Tian F
• Chen Y
• Ma X

• KMID: 2550339
• DOI: http://doi.org/10.4143/crt.2023.539

Abstract

Purpose
Although obesity is associated with numerous diseases, the risks of disease may depend on metabolically healthy status. Nevertheless, it is unclear to whether metabolically healthy status affects risk of gastrointestinal (GI) cancer in general Chinese population.
Materials and Methods
A total of 114,995 participants who met the criteria were included from the Kailuan Study. The study participants were divided into four groups according to body mass index (BMI)/waist circumference (WC) and metabolic status. Incident of GI cancer (esophageal cancer, gastric cancer, liver cancer, biliary cancer, pancreatic cancer, and colorectal cancer) during 2006-2020 were confirmed by review of medical records. The Cox proportional hazard regression models were used to assess the association metabolically healthy status with the risk of GI cancer by calculating the hazard ratios (HR) and 95% confidence interval (CI).
Results
During a mean 13.76 years of follow-up, we documented 2,311 GI cancers. Multivariate Cox regression analysis showed that compared with the metabolically healthy normal-weight group, metabolically healthy obese (MHO) participants demonstrated an increased risk of developing GI cancer (HR, 1.54; 95% CI, 1.11 to 2.13) by BMI categories. However, such associations were not found for WC category. These associations were moderated by age, sex, and anatomical site of the tumor. Individuals with metabolic unhealthy normal-weight or metabolic unhealthy obesity phenotype also have an increased risk of GI cancer.
Conclusion
MHO phenotype was associated with increased risk of GI cancer. Moreover, individuals who complicated by metabolic unhealthy status have an increased risk of developing GI cancer. Hence, clinicians should consider the risk of incident GI cancer in people with abnormal metabolically healthy status and counsel them about metabolic fitness and weight control.

Keyword

Metabolically healthy status; Gastrointestinal neoplasms; Cohort studies; Risk factors

Figure

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  Fig. 1. Flowchart of the study population. BMI, body mass index; DBP, diastolic blood pressure; FBG, fasting blood glucose; HDL, high density lipoprotein; SBP, systolic blood pressure; TG, triglyceride; WC, waist circumference; WHR, waist-hip ratio; WHtR, waist-to-height ratio.

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  Fig. 2. Dose-response relationship between body mass index/waist circumference level and gastrointestinal (GI) cancer. The association between body mass index and incident GI cancer among metabolically healthy (A) and unhealthy (B) participants, with reference BMI=28 kg/m2. The association between waist circumference level and incident GI cancer among metabolically healthy (C) and unhealthy (D) participants, with reference waist circumference=85 cm. The solid lines and shaded areas represent the hazard ratios and corresponding 95% confidence intervals. The models were adjusted for age, sex, educational level, drinking, smoking, physical exercise, family history of cancer, salt intake, high-sensitive C-reactive protein, and alanine transaminase. p-values for non-linearity were obtained using a chisquared test to compare nested models.

Reference

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