PhysiologyTier 1Medical Sciences concept

Obesity as a metabolic/endocrine risk factor for malignancy

Core concept

Adipose tissue is an endocrine organ, and three of its outputs are carcinogenic
- 1. Hyperoestrogenism - aromatase in adipose converts androstenedione -> oestrone, testosterone -> oestradiol
  - The dominant source of oestrogen after menopause; also dec SHBG -> inc free oestradiol
  - -> endometrial and postmenopausal breast cancer
- 2. Insulin resistance -> hyperinsulinaemia and inc bioavailable IGF-1
  - Insulin/IGF-1R -> PI3K-AKT-mTOR and RAS-MAPK -> proliferation, dec apoptosis
  - dec IGFBP-1 and -2 -> inc free IGF-1
- 3. Chronic low-grade inflammation ("metaflammation")
  - Adipocyte hypertrophy -> hypoxia, necrosis, crown-like structures of M1 macrophages
  - inc TNF-alpha, IL-6, leptin; dec adiponectin -> NF-kB and STAT3 activation
Site-specific mechanisms - GORD/Barrett's (mechanical) for oesophageal adenocarcinoma; bile acids and NAFLD-cirrhosis for liver; gut dysbiosis for colorectal

3 more sections, plus exam facts

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