Obesity, Bariatric Surgery, and Cancer Risk: Nutritional Perspectives and Long-Term Clinical Implications

Abstract

Obesity is recognized as a causal risk factor for the development of multiple cancers, with risk magnitude varying by tumor site, sex, life stage, and adipose tissue distribution. This narrative review synthesizes recent epidemiological evidence linking excess body fatness with cancer incidence and mortality and integrates the biological mechanisms that explain this association. Chronic low-grade inflammation, insulin resistance with compensatory hyperinsulinemia, dysregulation of adipose-derived hormones and sex steroids, impairment of anti-tumor immune responses, alterations in the gut microbiota, and remodeling of the tumor microenvironment collectively create conditions that favor tumor initiation and progression. Bariatric surgery is the most effective clinical intervention for achieving substantial and sustained weight loss in individuals with severe obesity, and growing evidence indicates that it is associated with a reduction in overall cancer risk and cancer-related mortality, particularly for malignancies strongly linked to obesity. However, the extent of this benefit differs by surgical technique and remains less consistent for colorectal cancer. Beyond metabolic improvements, bariatric surgery produces long-term changes in nutritional physiology that may also influence oncologic outcomes. Persistent deficiencies of micronutrients such as iron, folate, vitamin B12, vitamin D, and calcium can affect DNA synthesis, methylation, oxidative balance, and cellular repair. Altered protein and energy intake may contribute to loss of lean mass and reduced metabolic resilience, while changes in alcohol absorption and metabolism can increase systemic exposure to ethanol and its carcinogenic metabolites. In addition, bariatric surgery induces sustained remodeling of the gut microbiome and bile acid metabolism, which may further modulate tumorigenic signaling. Overall, the oncological impact of bariatric surgery reflects a balance between metabolic improvement and long-term nutritional management, underscoring the need for structured follow-up and targeted nutritional strategies to optimize cancer risk reduction.

Keywords: bariatric surgery; cancer risk; gut microbiota; inflammation; insulin resistance; micronutrient deficiencies; obesity.

Figure 1

Mechanistic pathways linking obesity to carcinogenesis. Created in BioRender. Reytor, C. (2026) https://BioRender.com/xq8i7fg. Obesity promotes carcinogenesis through six interconnected mechanisms: (1) chronic inflammation [52,53,54,55,56,57,58], (2) metabolic dysfunction [59,60,61,62,63,64,65,66,67,68], (3) hormonal imbalance [69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92], (4) immune suppression [93,94,95,96,97,98,99], (5) gut microbiota alterations [100,101,102,103,104,105,106,107,108,109], and (6) remodeling of the tumor microenvironment [110,111,112,113,114,115,116,117,118]. Hypertrophic and hypoxic adipocytes drive inflammatory signaling and endocrine disruption [54,55,56,57,58,69,70,71,72,73,74,75,76]; systemic insulin resistance enhances mitogenic pathways; impaired immune surveillance favors tumor escape [93,94,95,96,97,98,99]; and microbiota-derived endotoxins sustain systemic inflammation [100,101,102,103,104,105,106]. Several of these pathways intersect with modifiable nutritional and metabolic exposures discussed throughout the manuscript, underscoring their relevance for long-term risk modulation after bariatric surgery. Abbreviations: STAT3: Signal Transducer and Activator of Transcription 3; NF-κB: Nuclear Factor kappa-B; IGF-1: Insulin-like Growth Factor 1; PI3K/AKT/mTOR: Phosphoinositide 3-kinase/Protein Kinase B/Mammalian Target of Rapamycin; NK cells: Natural Killer cells; MDSCs: Myeloid-Derived Suppressor Cells; LPS: Lipopolysaccharides; ECM: Extracellular Matrix; VEGF: Vascular Endothelial Growth Factor; TNF-α: Tumor Necrosis Factor alpha; IL-6: Interleukin 6; (↑) indicate increased expression, levels, or activity; (↓) indicate decreased expression, levels, or activity.

Figure 2

Long-term Nutritional and Biological Mechanisms of BS Modulating Cancer Risk. Created in BioRender. Reytor, C. (2026) https://BioRender.com/j31kgzj.