Hormonal
Obesity promotes cancer development by increasing DNA damage and impairing DNA repair mechanisms, while simultaneously activating pro-survival signaling pathways that prevent the elimination of damaged cells.
Maintaining a healthy weight is a critical strategy for reducing cancer risk, not just for metabolic health. Obesity creates a biological environment that damages DNA and prevents the body from fixing those damages, while also protecting damaged cells from dying. Weight management interventions should be viewed as a direct cancer prevention strategy.
Obesity promotes accumulation of DNA damage and impairs DNA-repair capacity, thereby increasing genomic instability in affected tissues [31]. However, in non-obese contexts, excessive unrepaired DNA damage typically triggers a robust DNA-damage response (DDR) that results in cell-cycle arrest and apoptotic elimination of severely damaged cells; whereas, in obesity, pro-survival signalling can weaken this protective mechanism [32].
Why this rating
The paper cites multiple clinical studies, meta-analyses, and animal models supporting the link, though it is a review paper summarizing existing evidence rather than a single primary trial.
Source
Obesity and cancer: Relevance of DNA damage response
Bhavana Deshmukh et al. · Translational Oncology · 2026
DOI 10.1016/j.tranon.2025.102657
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