Abstract
BACKGROUND: To evaluate the associations between a new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) and extrahepatic cancers and compare with nonalcoholic fatty liver disease (NAFLD). METHODS: We enrolled 151,391 Chinese participants in the Kailuan cohort. Hepatic steatosis was detected by abdominal ultrasound. Fine and Gray competing risk regression models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI) between MAFLD and extrahepatic cancers. RESULTS: MAFLD was associated with increased risk of prostate (HR =1.49, 95% CI: 1.07-2.08) and obesity-related cancers, including thyroid (HR =1.47, 95% CI: 1.01-2.12), kidney (HR =1.54, 95% CI: 1.18-2.00), colorectal (HR =1.15, 95% CI: 0.98-1.34) and breast cancer (HR =1.31, 95% CI: 1.04-1.66). The results were consistent in NAFLD vs. non-NAFLD and MAFLD-NAFLD vs. neither FLD. Compared with the neither FLD group, the NAFLD-only group had a higher risk of extrahepatic cancers (HR =1.57, 95% CI: 1.18-2.09), esophageal (HR =5.11, 95% CI: 2.25-11.62), and bladder cancer (HR =3.36, 95% CI: 1.23-9.17). The additional risk of extrahepatic cancers (HR =1.42, 95% CI: 1.17-1.73), esophageal (HR =4.37, 95% CI: 2.55-7.49), and breast cancer (HR =1.99, 95% CI: 1.01-3.92) was observed in MAFLD with metabolic dysregulation, and kidney (HR =1.83, 95% CI: 1.38-2.43), prostate (HR =1.46, 95% CI: 1.00-2.14) and breast cancer (HR =1.33, 95% CI: 1.02-1.74) was observed in MAFLD with overweight and metabolic dysregulation, as well as colorectal (HR =1.45, 95% CI: 1.07-1.96) and prostate cancer (HR =2.44, 95% CI: 1.42-4.21) in MAFLD with three risk factors. Additionally, MAFLD with excessive alcohol consumption would increase extrahepatic cancers (HR =1.14, 95% CI: 1.01-1.29) and breast cancer (HR =7.27, 95% CI: 2.33-22.69) risk. CONCLUSIONS: MAFLD and NAFLD shared similar excessive risks of obesity-related cancers, suggesting a driving role of FLD in these cancers. Metabolic dysregulation beyond obesity may play additional kidney, colorectal, and prostate cancer risks in MAFLD patients. It may be helpful in the clinic to relieve symptoms by treating metabolic disorders and preventing adverse outcomes of extrahepatic cancers.