Obesity and cancer risk

Obesity (1)

• is associated with increased risk of cancer, including:
  • endometrial,
  • oesophageal,
  • gastric,
  • kidney,
  • colorectal,
  • liver,
  • gallbladder,
  • pancreas, prostate,
  • postmenopausal breast,
  • ovarian, and
  • thyroid cancers
• in observational studies, patients who lost more than 10% of body weight through bariatric procedures (n = 30 318) or with glucagon-like peptide 1 receptor agonists (n = 1 651 452) had modest reductions in obesity-associated cancer incidence (absolute change, −0.02% to −0.5%)

Pathophysiology of obesity and cancer link (1):

• obesity and overweight are characterized by excess accumulation of adipose tissue, which disrupts its primary function of energy storage
  • resultant excess energy, in the form of free fatty acids, is transferred to developing cancer cells and stimulates cancer development through genomic instability caused by oxidative stress and DNA damage
  • other features of adipose tissue contributing to cancer development include inflammation and altered hormone production such as:
    • increased oestrogens and leptin and decreased adiponectin
    • systemic elevations in inflammatory mediators, such as prostaglandin E₂, cytokines interleukin 1β and interleukin 6, and tumor necrosis factor α

• these mediators promote tumor growth directly or indirectly by stimulating oestrogen biosynthesis
  • can promote proliferation of hormone-sensitive cancers such as breast, ovarian, and endometrial cancer, or
  • by suppressing immune-mediated elimination of developing cancer cells through accumulation of myeloid-derived suppressor cells and reductions in the amount and function of cytotoxic T cells and natural killer cells

• inflammation and oxidative stress are also stimulated by
  • obesity-associated depletion of gut commensal bacteria species (eg, Akkermansia muciniphila) and
  • overgrowth of bacterial populations associated with cancer development in preclinical models (eg, Bilophila).

With respect to obesity and colorectal cancer (CRC) risk (2):

• central obesity is a much stronger predictor of CRC and may account for most of the CRC risk linked to obesity
• findings also emphasize the need for incorporating measures such as WHR (waist hip ratio) alongside BMI in clinical practice to improve obesity prevention and management

Reference:

1. Shen S, Brown KA, Green AK, Iyengar NM. Obesity and Cancer: A Translational Science Review. JAMA. Published online March 09, 2026.
2. Safizadeh, F., Mandic, M., Schöttker, B. et al. Central obesity may account for most of the colorectal cancer risk linked to obesity: evidence from the UK Biobank prospective cohort. Int J Obes (2024).