Novel perspectives on the link between obesity and cancer risk: from mechanisms to clinical implications

Obesity, recognized as a complex and growing health issue, is associated with an increased risk of various cancers. A comprehensive review provides insights into the mechanisms linking obesity to cancer risk and discusses potential clinical implications. Inflammation, hormonal imbalances, gut microbiota dysregulation, adipokine level disruptions, and physical and biochemical stimuli are identified as key mechanisms through which obesity influences cancer development. Chronic low-grade inflammation in adipose tissue, marked by increased proinflammatory immune cell infiltration and cytokine release, is a significant characteristic of obesity and plays a role in carcinogenesis. Hormonal disturbances, such as elevated estrogen levels, contribute to the development of obesity-related cancers, especially in postmenopausal women. The gut microbiota is also dysregulated in obesity, promoting inflammation and carcinogenesis. Adipose tissue, an active endocrine organ, secretes adipokines like leptin and adiponectin, which can either promote or inhibit cancer development when their levels are altered in obesity. Additionally, physical stimuli such as increased abdominal pressure and interstitial fibrosis contribute to the risk of obesity-associated cancer.

Prevention strategies for obesity-related cancers are highlighted, emphasizing the importance of weight management through dietary interventions, physical activity, bariatric surgery, and pharmacotherapy. Dietary modifications, including low-fat, low-carbohydrate, and Mediterranean diets, reduce cancer risk by alleviating inflammation and oxidative stress. Regular physical activity normalizes immune metabolism and mitigates chronic inflammation, reducing the risk of obesity-associated cancers. Bariatric surgery has been shown to significantly decrease cancer incidence post-surgery. Pharmacological interventions, including weight loss medications and drugs targeting oncogenic pathways, offer a non-surgical approach to cancer prevention in obese individuals.

The review underscores the need for a deeper understanding of the mechanisms linking obesity and cancer to develop personalized prevention and treatment strategies. It raises questions about the distinct effects of acquired and hereditary obesity on cancer risk, the influence of aging on these effects, and the potential vicious cycle between worsening obesity, gut microbiota dysbiosis, and cancer promotion. Further research is called for to explore these complex interactions and to evaluate the differential effects of various intervention strategies on the risk of developing different types of obesity-related cancers.

In summary, the review thoroughly examines the connection between obesity and cancer, outlining specific mechanisms and potential intervention strategies. It emphasizes the importance of targeting obesity-associated oncogenic pathways to prevent cancer development and suggests that a multifaceted approach, combining lifestyle modifications with pharmacological interventions, may be most effective in reducing the incidence of obesity-related cancers. By shedding light on the complex interplay between obesity and cancer, this review contributes to the development of more effective, personalized, and precise intervention strategies for obese patients, ultimately aiming to reduce the burden of obesity-related cancers.