Table 2.

Putative mechanisms linking NAFLD and extra-hepatic cancers.

Mechanism	Effects	Extra-Hepatic Site
Insulin resistance
↑ IGF-1 axis	Proliferative and anti-apoptotic effects	Prostate/colorectal/lung/Breast cancers, Barrett’s esophagus, esophageal adenocarcinoma
Dysfunctional adipose tissue
↓ adiponectin/caspase activation ↓ adiponectin/TNF-α ↑ leptin/MAPK ↑ resistin/NF-κB	Anti-apoptotic effects Proliferation and angiogenesis Invasiveness, motility, lamellipodia formation	Gastrointestinal and extra-intestinal cancer Gastrointestinal and extra-intestinal cancer Colon/breast cancer, Barrett’s esophagus, esophageal adenocarcinoma Breast/gastrointestinal and non-small cell lung cancers
Inflammation
IL-6/JAK/STAT3 and IL-6/MAPK TNF-α/Wnt/β-catenin	Proliferation Angiogenesis, differentiation and metastasis development	Renal/gastric/colorectal cancers Colorectal cancer
Gut microbiota
MAMPs/TLRs Inflammasome-derived IL-18	Inflammation Anti-apoptotic effects	Colon cancer Colon cancer

IGF-1, insulin growth factor-1; IL, interleukin; MAMPs, microorganism-associated molecular patterns; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-κ B; STAT3, signal transducer and activator of transcription 3; TLRs, toll-like receptors; TNF-α, tumor necrosis factor-α.