Obesity and Cancer

Krasimira Aleksandrova, Marta Stelmach-Mardas, Sabrina Schlesinger, Aleksandrova, Krasimira, Stelmach-Mardas, Marta, Schlesinger, Sabrina

Tobias Pischon, Katharina Nimptsch

Obesity and related metabolic disorders have become globally prevalent posing a challenge for the chronically damaged liver and predisposing the development and progression of cancer. The rising phenomenon of "obesity epidemic" may provide means for understanding why liver cancer is one of the few malignancies with rising incidence in developed countries over the last decades. Non-alcoholic fatty liver disease associated with obesity, insulin resistance, and type 2 diabetes is an increasingly recognized trigger for liver cancer in Western populations characterized by low prevalence of established risk factors for liver cancer such as viral hepatitis and hepatotoxin exposure. Accumulating evidence has established an association between higher body mass index as an indicator of general obesity and higher risk of primary liver cancer. The associations are stronger in men, in patients with underlying liver disease and in white ethnic groups. Abdominal obesity, weight gain in adult life and metabolic factors related to visceral fat accumulation were also suggested as important risk factors for liver cancer; however, more studies are needed to evaluate these associations. The association of obesity and metabolic parameters with liver cancer survival remains controversial. It is unclear which exact mechanisms could provide links between obesity and liver cancer risk. Recent evidence has implicated several molecular pathways in obesity-associated liver cancer. These include insulin resistance leading to increased levels of insulin and insulin-like growth factors, chronic inflammation, adipose tissue remodeling, pro-inflammatory cytokine and adipokine secretion, and altered gut microbiota. These mechanisms coincide with inflammatory and metabolic processes occurring in non-alcoholic fatty liver disease predisposing cancer development and progression. In the context of the current evidence, better understanding of the role of obesity and related metabolic factors may help in improving current strategies for liver cancer prevention.