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

**Authors:** Claudia Reytor-González, Gerardo Sarno, Martha Montalvan, Ludovica Verde, Giuseppe Annunziata, Luigi Barrea, Giovanna Muscogiuri, Daniel Simancas-Racines

PMC · DOI: 10.3390/nu18040685 · 2026-02-20

## TL;DR

Obesity increases cancer risk, and bariatric surgery can reduce it, but long-term nutritional changes must be managed to optimize outcomes.

## Contribution

This review integrates recent evidence on how obesity and bariatric surgery influence cancer risk through metabolic and nutritional mechanisms.

## Key findings

- Bariatric surgery reduces overall cancer risk and mortality, especially for obesity-linked cancers.
- Micronutrient deficiencies after surgery may affect DNA synthesis and cellular repair.
- Gut microbiome and bile acid changes post-surgery may modulate tumor development.

## 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.

## Linked entities

- **Chemicals:** ethanol (PubChem CID 702)
- **Diseases:** obesity (MONDO:0011122), cancer (MONDO:0004992), colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, ESR2 (estrogen receptor 2) [NCBI Gene 2100] {aka ER-BETA, ESR-BETA, ESRB, ESTRB, Erb, NR3A2}, RETN (resistin) [NCBI Gene 56729] {aka ADSF, FIZZ3, RENT, RETN1, RSTN, XCP1}, NAMPT (nicotinamide phosphoribosyltransferase) [NCBI Gene 10135] {aka 1110035O14Rik, PBEF, PBEF1, VF, VISFATIN}, RARRES2 (retinoic acid receptor responder 2) [NCBI Gene 5919] {aka HP10433, TIG2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, AKR1A1 (aldo-keto reductase family 1 member A1) [NCBI Gene 10327] {aka ALDR1, ALR, ARM, DD3, HEL-S-6}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, SERPINA12 (serpin family A member 12) [NCBI Gene 145264] {aka OL-64}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, ITLN1 (intelectin 1) [NCBI Gene 55600] {aka HL-1, HL1, INTL, ITLN, LFR, hIntL}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, INSR (insulin receptor) [NCBI Gene 3643] {aka CD220, HHF5}, SHBG (sex hormone binding globulin) [NCBI Gene 6462] {aka ABP, SBP, TEBG}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}
- **Diseases:** rectosigmoid tumors (MESH:D011350), hormone-dependent malignancies (MESH:D009376), GERD (MESH:D005764), excess (MESH:D006970), injury to (MESH:D014947), anemia (MESH:D000740), pancreatic ductal adenocarcinoma (MESH:D021441), Chronic inflammation (MESH:D007249), breast, endometrial, colorectal, and pancreatic malignancies (MESH:C537262), Sarcopenia (MESH:D055948), steatotic liver disease (MESH:D008107), fibrosis (MESH:D005355), cardiometabolic disease (MESH:D024821), hypocalcemia (MESH:D006996), immune impairment (MESH:D020274), thyroid cancer (MESH:D013964), polycystic ovary syndrome (MESH:D011085), tumorigenic (MESH:D002471), malabsorption (MESH:D008286), malignant meningioma (MESH:D008579), cervical cancer (MESH:D002583), Micronutrient Deficiencies (MESH:D007153), carcinogenic (MESH:D011230), Chronic hyperinsulinemia (MESH:D006946), malnutrition (MESH:D044342), death (MESH:D003643), EC (MESH:D016889), BS (MESH:D000267), breast carcinogenesis (MESH:D061325), Colorectal cancer (MESH:D015179), alcohol (MESH:D000437), folate (MESH:C562799), PC (MESH:D010190), cardiovascular disease (MESH:D002318), multiple myeloma (MESH:D009101), infection (MESH:D007239), Dysbiosis (MESH:D064806), Immune Dysfunction (MESH:D007154), endocrine disruption (MESH:D004700), Cancers (MESH:D009369), Rectal adenocarcinoma (MESH:D000230), vascular dysfunction (MESH:D002561), Weight (MESH:D015431), liver fibrosis (MESH:D008103), ESCC (MESH:D000077277), IR (MESH:D007333), rectal cancer (MESH:D012004), gallbladder cancer (MESH:D005706), steatohepatitis (MESH:D005234), mammary tumor (MESH:D015674), lean mass loss (MESH:D013851), GC (MESH:D013274), endometrial hyperplasia (MESH:D004714), skin cancers (MESH:D012878), abdominal adiposity (MESH:D000007), ODDS (MESH:D009765), BC (MESH:D001943), Excess adiposity (MESH:D018205), hypoxic (MESH:D002534), Deficiencies in vitamin B12 (MESH:D014806)
- **Chemicals:** tyramine (MESH:D014439), 25(OH)D (-), BA (MESH:D001647), Vitamin D (MESH:D014807), 25-hydroxyvitamin D (MESH:C104450), zinc (MESH:D015032), sodium (MESH:D012964), butyrate (MESH:D002087), thiamine (MESH:D013831), lithocholic acid (MESH:D008095), levonorgestrel (MESH:D016912), carbon (MESH:D002244), carbohydrate (MESH:D002241), selenium (MESH:D012643), B12 (MESH:C034730), Calcium citrate (MESH:D019355), luminal (MESH:D010634), LPS (MESH:D008070), Iron (MESH:D007501), lipid (MESH:D008055), nucleotide (MESH:D009711), vitamin B12 (MESH:D014805), vitamin C (MESH:D001205), Alcohol (MESH:D000438), Progesterone (MESH:D011374), copper (MESH:D003300), acetaldehyde (MESH:D000079), ethanol (MESH:D000431), glucose (MESH:D005947), magnesium (MESH:D008274), SCFA (MESH:D005232), BAs (MESH:D001464), Folate (MESH:D005492), BAC (MESH:D000067401), Calcium (MESH:D002118)
- **Species:** Homo sapiens (human, species) [taxon 9606], Faecalibacterium prausnitzii (species) [taxon 853], gut metagenome (species) [taxon 749906], Nicotiana tabacum (American tobacco, species) [taxon 4097]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12943767/full.md

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Source: https://tomesphere.com/paper/PMC12943767