Obesity is a major health concern that goes beyond just weight. It is linked to a higher chance of developing cancer. This connection is not just about how much someone weighs. It is about how fat cells behave and interact with other cells in the body. This interaction can lead to cancer in various ways.

First, let's talk about hormones. Obesity can cause hormonal imbalances. For example, higher estrogen levels can increase the risk of breast and endometrial cancers. Insulin resistance is another issue. It can activate certain pathways that promote colorectal cancer. These hormonal changes are just one piece of the puzzle.

Inflammation is another key factor. Obesity often leads to chronic low-grade inflammation. This inflammation, along with metabolic dysfunction and lack of oxygen in expanding fat tissue, can contribute to several types of cancer. These include pancreatic, esophageal, colorectal, renal, and liver cancers.

Recent studies have uncovered new mechanisms. The secretions from fat tissue, the transfer of lipids and RNA via extracellular vesicles, resistance to a type of cell death called ferroptosis, and changes in metabolism can all create an environment that supports tumor growth. These factors can make it easier for cancer to develop and progress.

Even after weight loss, the risk of cancer can persist. This is due to something called epigenetic memory. Certain changes in the body's cells can stick around, even if the weight comes off. These changes can include modifications to histones and DNA, as well as RNA changes, particularly involving the FTO gene.

There are also emerging pathways that highlight obesity's role in cancer. For instance, the VHL-HIF axis, the inhibition of PRDM16/UCP1, the upregulation of FABP4 driven by STAT3, and the signaling of YAP/TAZ are all areas of interest. These pathways show how complex the relationship between obesity and cancer truly is.

To tackle this issue, future research should focus on several areas. The effects of weight-loss drugs on cancer pathways need to be studied. There is also a need for more diverse demographic representation in studies. Developing biomarkers for adiposity could also be beneficial. Integrating advanced techniques like Mendelian randomization, multi-omics, and artificial intelligence could reveal new therapeutic targets.

A comprehensive prevention strategy is crucial. This strategy should combine lifestyle changes, medications, and diagnostics driven by biomarkers. By addressing obesity from multiple angles, it is possible to reduce the burden of obesity-related cancers and improve patient outcomes.

EPIGENETIC MODIFICATIONS IN OBESITY

Obesity's Hidden Impact on Cancer Risk

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