Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management

Obesity is a common disease associated with multiple chronic illnesses (coronary artery disease, diabetes mellitus, hypertension, osteoarthritis, sleep and mental disorders) and an increasing number of solid and hematologic malignancies. It is linked to breast, colorectal, esophageal, stomach, gallbladder, uterine, pancreatic, ovarian and other cancers. The relationship is complex: obesity increases not only cancer risk but also recurrence and mortality in survivors, supporting early intervention and weight management as integral to cancer care. Recent evidence has strengthened the association between obesity and inferior cancer outcomes, and newer, more effective weight-management drugs have been approved. This review updates definitions and measurement of obesity, epidemiology of obesity and cancer, mechanisms linking obesity to carcinogenesis and progression, the impact of obesity on outcomes and treatment-related complications, and the management of obesity in cancer survivors, ending with ongoing clinical trials.

This narrative review synthesizes epidemiologic and mechanistic evidence linking excess adiposity to cancer incidence, recurrence, and mortality across multiple tumor sites. It summarizes global and U.S. burden estimates (4–8% of all cancers attributable to obesity), highlights IARC 2020 conclusions implicating 13 cancers with strong evidence, and reports dose–response risk increases per 5 kg/m² BMI. Mechanistic literature is reviewed on estrogen biosynthesis via adipose aromatase, hyperinsulinemia/IGF-1 signaling, and chronic inflammation/adipokines, as well as extracellular matrix remodeling, immune dysregulation, and microbiome changes. Site-specific outcome data are synthesized for breast (including triple-negative), colorectal, pancreatic, endometrial, and prostate cancers. The review covers treatment-related toxicity evidence (surgery, radiation, chemotherapy cardiotoxicity and neuropathy) and the effects of dosing practices (dose capping). It evaluates lifestyle, pharmacological (GLP-1 analogues), and surgical (bariatric) weight-loss interventions, and outlines ongoing randomized trials (e.g., BWEL, LIVES, CHALLENGE, INTERVAL) targeting weight loss and exercise in cancer survivorship.

A literature search was conducted using PubMed and Google Scholar. Clinical practice guidelines, position papers, and reference lists of relevant articles were also reviewed. Given the broad scope, no formal systematic search strategy was implemented. The search was largely restricted to English-language publications up to September 2022 and focused on studies addressing epidemiology, mechanisms of carcinogenesis in obesity, incidence and recurrence risks, and obesity management. Multiple targeted searches combining terms related to 'obesity' and 'cancer' were performed independently for each section. Senior authors reviewed citations and section content. Most clinical evidence derives from meta-analyses, systematic reviews of observational studies, or pooled trial analyses.

- Global burden: Approximately 4–8% of all cancers are attributable to obesity, with higher proportions in high-income countries. - Risk by site (examples per 5 kg/m² BMI increase): endometrial cancer RR ≈1.59 (women); esophageal adenocarcinoma RR ≈1.51 (both sexes); kidney cancer RR ≈1.34 (women), 1.24 (men); postmenopausal breast cancer RR ≈1.12 (women); hepatocellular carcinoma RR ≈1.12–1.19; pancreatic adenocarcinoma RR ≈1.10–1.13; colon cancer RR ≈1.09 (women), 1.24 (men); rectal cancer RR ≈1.02 (women), 1.09 (men); ovarian cancer RR ≈1.06 (women). - Mortality and recurrence across cancers: Obesity associated with a 14% higher overall mortality (HR 1.14; 95% CI 1.09–1.19), 17% higher cancer-specific mortality (HR 1.17; 1.12–1.23), and 13% higher recurrence risk (HR 1.13; 1.07–1.19). - Breast cancer: Obesity linked to 35% higher breast cancer-specific and 41% higher all-cause mortality in survivors; in triple-negative disease, overweight associated with worse DFS (HR 1.26) and OS (HR 1.29). Post-diagnostic weight gain (≥10%) increases all-cause mortality (HR 1.23); weight gain after diagnosis overall associated with 12% higher all-cause mortality. - Colorectal cancer: Pre-diagnostic obesity increases CRC-specific mortality by 22% and all-cause mortality by 25%; post-diagnosis BMI ≥35 associated with 13% higher all-cause mortality; overall ≈14% increases in CRC-specific and all-cause mortality with obesity. - Pancreatic cancer: Obesity associated with 28% higher pancreatic cancer mortality; every 1 kg/m² BMI increase linked to 10% higher mortality. - Endometrial cancer: Obesity associated with 34% higher all-cause mortality and 28% higher recurrence. - Prostate cancer: Obesity increases prostate cancer-specific mortality by 19% and all-cause mortality by 9%; per 5 kg/m² BMI increases biochemical recurrence by 21%, cancer-specific mortality by 9%, all-cause mortality by 3%. - Mechanisms: Elevated estrogen via adipose aromatase, hyperinsulinemia/IGF-1, chronic inflammation with altered adipokines (↑leptin, ↓adiponectin), ECM remodeling, immune dysregulation, and microbiome alterations plausibly drive carcinogenesis and progression; central/visceral adiposity particularly adverse. - Treatment-related adverse effects: Higher risks of lymphedema after breast cancer surgery/radiation (OR ~2.9–3.6), chemotherapy-induced neuropathy with taxanes/platinum, cardiotoxicity with anthracyclines/trastuzumab (47% increased risk), more acute radiation dermatitis (BMI >25 → 11% higher risk), and more surgical complications. - Treatment selection/dosing: Dose capping of chemotherapy in obese patients is common but discouraged by guidelines; underdosing may worsen prognosis. - Weight-loss interventions: Lifestyle programs combining diet, structured exercise, and behavioral therapy most effective for weight loss and improving insulin resistance, sex hormones, leptin, and inflammatory markers. Liraglutide 3.0 mg daily for 56 weeks led to ≥5% weight loss in 63.2% (vs 27.1% placebo) and >10% loss in 33.1% (vs 10.6%); semaglutide weekly is effective as well. Bariatric surgery associated with ~55% reduction in overall cancer risk, with larger benefits in obesity-related cancers (~38% risk reduction).

The review consolidates epidemiologic and mechanistic data demonstrating that excess adiposity causally contributes to the incidence of multiple cancers and adversely affects prognosis through hormonal (estrogen), metabolic (insulin/IGF-1), and inflammatory pathways, with central adiposity exerting notable risk. The consistent elevation in overall and cancer-specific mortality and recurrence across multiple tumor types underscores obesity as a critical, modifiable factor in oncology. Clinical implications include recognizing obesity-related increases in surgical, radiation, and systemic therapy toxicities, and avoiding chemotherapy dose capping to preserve curative intent, particularly for early-stage and chemosensitive malignancies. Integrating comprehensive weight management—structured exercise, dietary energy restriction, and behavioral strategies—into survivorship care can improve metabolic biomarkers and quality of life and may improve disease outcomes. Pharmacologic agents (GLP-1 receptor agonists) and bariatric surgery offer effective options for selected survivors, though long-term oncologic safety data remain limited. Ongoing randomized trials will clarify the impact of intentional weight loss and physical activity on cancer recurrence and survival, informing future guideline-directed care.

Obesity is a major, preventable global health issue strongly linked to increased incidence and worse outcomes in several cancers (e.g., breast, colorectal, endometrial, esophageal, pancreatic, renal, hepatic, stomach, gallbladder, ovarian, thyroid, multiple myeloma, and meningioma). Mechanisms involve adipokines, inflammation, ECM remodeling, altered fatty acid metabolism, and insulin-like growth factors and estrogen. Weight-reduction strategies—regular exercise, dietary modification, and behavioral therapy—are key components of cancer care for survivors with excess body weight and may reduce cancer-specific and overall mortality. Additional evidence is needed regarding the long-term efficacy and safety of pharmacologic and surgical weight-loss interventions in cancer survivors.

- Narrative review without a formal systematic search; reliance on observational studies and meta-analyses introduces potential bias and residual confounding. - Heterogeneity across cancer types and subtypes complicates causal inference and generalizability. - Common use of a fixed BMI threshold (≥30 kg/m²) may misclassify risk; limited data on timing/duration of obesity and central adiposity versus overall adiposity. - Incomplete adjustment for psychosocial, genetic, environmental, and behavioral factors in many studies. - Anthropometric measures have limitations; more accurate assessments of body fat and distribution (e.g., DEXA, CT/MRI) are not routinely used. - Long-term sustainability of weight loss from lifestyle interventions is uncertain; long-term oncologic safety data for GLP-1 analogues and bariatric surgery in survivors are limited.