Metabolic dysfunction-associated fatty liver disease and the risk of 24 specific cancers

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health issue closely associated with multiple metabolic dysfunctions. The association between MAFLD and cancer risk is yet unknown.

Methods: UK Biobank study participants were diagnosed for the presence of MAFLD at baseline. A multivariable Cox regression model was performed to examine the associations of MAFLD with incident events in 24 specific cancers.

Results: We included 352,911 individuals (37.2% with MAFLD), among whom 23,345 developed cancers. Compared with non-MAFLD, MAFLD was significantly associated with 10 of the 24 examined cancers, including corpus uteri (hazard ratio [HR] = 2.36, 95% CI 1.99-2.80), gallbladder (2.20, 1.14-4.23), liver (1.81, 1.43-2.28), kidney (1.77, 1.49-2.11), thyroid (1.69, 1.20-2.38), esophagus (1.48, 1.25-1.76), pancreas (1.31, 1.10-1.56), bladder (1.26, 1.11-1.43), breast (1.19, 1.11-1.27), and colorectal and anus cancers (1.14, 1.06-1.23). The associations of MAFLD with liver, esophageal, pancreatic, colorectal and anal and bladder cancers and malignant melanoma were strengthened in males, and associations with kidney, thyroid, and lung cancers were increased in females. The associations of MAFLD with the risk of liver, kidney, and thyroid cancers remained significant after further adjusting for the waist circumference or body mass index and the number of metabolic syndrome components based on the main models. The risk-increasing allele of PNPLA3 rs738409 significantly amplified the association of MAFLD with the risk of liver and kidney cancers.

Conclusion: MAFLD is associated with an increased risk of a set of cancers, but the effect substantially varies by site. MAFLD deserves higher priority in the current scheme of cancer prevention.