Dairy consumption and hepatocellular carcinoma risk

Area of Science:

• Hepatology and Cancer Research
• Nutritional Epidemiology
• Molecular Biology

Background:

• Hepatocellular carcinoma (HCC) pathogenesis is influenced by dietary factors.
• Mechanistic target of rapamycin complex 1 (mTORC1) hyperactivity is a key feature in HCC development.
• Milk and dairy consumption patterns have changed significantly in Western countries.

Purpose of the Study:

• To review epidemiological and translational evidence linking milk/dairy intake to HCC pathogenesis.
• To elucidate the molecular mechanisms by which milk components may promote HCC.
• To explore potential preventive roles of specific dairy products like yogurt.

Main Methods:

• Review of epidemiological studies from the US and Europe.
• Analysis of translational research on mTORC1 signaling pathways.
• Investigation of the role of milk proteins, branched-chain amino acids (BCAAs), and exosomes in liver cancer.

Main Results:

• Total dairy, milk, and butter intake are identified as independent risk factors for HCC.
• Milk proteins activate hepatic IGF-1 and BCAAs, leading to mTORC1 activation.
• Milk-derived exosomes carry oncogenic microRNAs (miR-21, miR-155) that promote HCC via mTORC1 signaling.
• Yogurt may prevent HCC due to lactobacilli degrading BCAAs and milk exosomes.

Conclusions:

• Milk and dairy intake, excluding yogurt, represent critical risk factors for HCC.
• Dietary BCAAs and milk exosomes synergistically promote HCC by overstimulating hepatic mTORC1.
• A vegetable-based diet restricting total animal protein is recommended for HCC prevention.