Metabolic dysfunction-associated steatotic liver disease and the consequence of extra-hepatic malignancy

Table 1 Gastrointestinal extrahepatic malignancies in metabolic dysfunction-associated steatotic liver disease: Cancer type, key studies, risk estimates, proposed mechanisms, and trends

Cancer type	Ref.	Risk estimate (HR or OR)	Proposed mechanisms	Trend/notes
Colorectal cancer	Wu et al[33], 2026 (international Delphi consensus, Gut); Mantovani et al[12], 2022 (meta-analysis, Gut); Zhou et al[37], 2024 (meta-analysis, n ≈ 16.7M); Allen et al[35], 2019 (community cohort, J Hepatol); Azimi et al[34], 2025 (meta-analysis, n > 56M)	HR 1.33 (Zhou et al[37] meta-analysis); approximately 1.5-2-fold (Mantovani et al[12], 2022); OR 1.37 (Azimi et al[34], 2025)	Gut dysbiosis; secondary bile acid alterations; hyperinsulinemia; mucosal inflammation; IGF-1 axis activation	Rising; strongest GI cancer association; independent of obesity and T2DM
Pancreatic cancer	Mantovani et al[12], 2022 (meta-analysis, Gut); Zhou et al[37], 2024 (meta-analysis, Eur J Clin Invest); Thomas et al[9], 2024 (review, Lancet GE&H); Thomas et al[10], 2022 (meta-analysis, Eur J Cancer); Mantovani et al[36], 2024	HR 1.41 (Zhou et al[37] meta-analysis); approximately 1.5-2-fold (Mantovani et al[12], 2022)	Insulin resistance; visceral adiposity; acinar inflammation; shared T2DM pathway	Rising; evidence strengthening with larger population cohorts
Esophageal/gastric cancer	Zou et al[40], 2023 (meta-analysis); Mantovani et al[12], 2022 (meta-analysis, Gut); Zhou et al[37], 2024 (meta-analysis); Thomas et al[9], 2024 (Lancet GE & H); Mantovani et al[36], 2024	Gastric: HR 1.47 (Zhou et al[37]), RR 1.49 (Zou et al[40]); esophageal: RR 1.76 (Zou et al[40]), null in Zhou et al[37] meta-analysis	GERD; Barrett’s esophagus; visceral adiposity; reflux-related mucosal injury	Moderate; gastric cancer signal more consistent than esophageal across meta-analyses
Biliary tract cancer (gallbladder/cholangiocarcinoma)	Park et al[41], 2021 (nationwide Korean cohort, n ≈ 8.1M, Eur J Cancer); Zhou et al[37], 2024 (meta-analysis); Mantovani et al[36], 2024	BTC overall: AHR 1.28 (Park et al[41], 2021), HR 1.27 (Zhou et al[37]); cholangiocarcinoma aHR 1.33; gallbladder aHR 1.14	Biliary stasis; cholelithiasis; chronic biliary inflammation	Emerging; cholangiocarcinoma shows the stronger signal; gallbladder signal weaker; Western validation limited

HR: Hazard ratio; OR: Odds ratio; aHR: Adjusted hazard ratio; RR: Relative risk; IGF-1: Insulin-like growth factor-1; T2DM: Type 2 diabetes mellitus; GERD: Gastroesophageal reflux disease; BTC: Biliary tract cancer; GI: Gastrointestinal.