Liu Z, Lin C, Suo C, et al. - In this study, metabolic dysfunction-associated fatty liver disease (MAFLD) was found to be linked with an elevated risk of a set of cancers, but the impact substantially differed by site. MAFLD merits higher priority in the current scheme of cancer prophylaxis.

• This study involved 352,911 UK Biobank participants (37.2% with MAFLD), among whom 23,345 developed cancers.

• MAFLD was identified to be significantly linked with 10 of the 24 examined malignancies, including corpus uteri (hazard ratio, 2.36), gallbladder (2.20), liver (1.81), kidney (1.77), thyroid (1.69), esophagus (1.48), pancreas (1.31), bladder (1.26), breast (1.19), and colorectal and anus cancers (1.14), vs non-MAFLD.

• In men, the links of MAFLD with liver, esophageal, pancreatic, colorectal and anal and bladder cancers and malignant melanoma were strengthened, and links with kidney, thyroid, and lung cancers were elevated in women.

• The relations of MAFLD with the risk of liver, kidney, and thyroid cancers continued to be significant following further adjustments for the waist circumference or BMI and the number of metabolic syndrome components based on the main models.

• Risk-increasing allele of PNPLA3 rs738409 was shown to significantly amplify the relationship of MAFLD with the risk of liver and kidney malignancies.