Obesity as a major risk factor for cancer

In the sedentary era, weight gain is becoming a serious preventable risk factor for increased body mass index which strongly correlates with enhanced cancer threat.

Epidemiology

As reported cancers of endometrial, oesophageal adenocarcinoma, colorectal, postmenopausal breast, prostate & renal are caused due to surplus weight. The mechanism behind obesity and cancer partnership. The body’s lean shape is regulated by the delicate balance between adipocytes & immune cells. Chronic nutrient overload leads to adipocyte hypertrophy, mitochondrial dysfunction, increased oxidative & endoplasmic reticulum stress, proinflammatory signalling, adipokine secretion & cell death. Collectively instigate enhanced secretion of proinflammatory factors, dysregulated systemic metabolism, tumour growth, metastasis & progression. 

Changes at the tissue level

 • Alteration in an adipose stromovascular fraction
 • Reduction in anti-inflammatory Treg & TH2 cells 
 • Increase in proinflammatory TH1 & CD8+T cells 
 • Variation in M2 to M1 macrophages

How adipose-derived factors affect cancer 

1. Adipokines - Weight gain alters the interaction between adipocytes, adipokine production 
2. Adiponectin- Obesity triggers adiponectin reduction & causes a mutation in adiponectin receptors (ADIPOR1 & ADIPR2) 
3. Leptin -Excessive weight facilitates leptin resistance & hyperlipidaemia, enables cell proliferation, migration, invasion responses, and tumour development
4. Estrogen- Increased weight fosters adipose-derived aromatase activity, estrogen production, systemic estrogen bioavailability, adipose-derived proinflammatory factors (IL-1β, IL-6, prostaglandin E2, and TNFα), liver-derived insulin growth factor 1 (IGF-1)
5. IL-6 and TNFα- Obesity-induced excess IL-6 and TNFα levels encourage cellular transformation, proliferation, invasion, angiogenesis, metastasis, cancer cell proliferation, survival & angiogenesis.
6. IL-1β- Heavy weight increases free fatty acid, cholesterol, blood sugar, and free radical’s levels stimulating tumour expression of IL-1β, NOD-like receptor family, pyrin domain containing 3 (NLRP3) & inflammasome activity
7. Osteopenia-Neoplastic transformation, cancer cell survival & metastasis progression enhances due to obesity-driven osteopenia phosphoprotein
8. YKL-40- Excessive obesity with diabetes generate YKL-40, cancer cell proliferation, angiogenesis, and extracellular matrix remodelling
9. PAI-1- Advancing obesity increases PAI-1 (serine protease inhibitor), cancer cell invasion, metastasis & tumours
10. Endotrophic -Increased adipose tissue promotes endotrophic production, activates TGF-β signalling, tumour cell growth & metastasis

Metabolic dysregulation & amp; life-threatening obesity-related outcomes 

 • Central obesity causes insulin resistance, dyslipidaemia, hyperglycaemia & metabolic dysfunction
 • Visceral adipose tissue aggravates the abdominal cavity’s momentum & produces more proinflammatory factors

Effect of Weight loss effect on cancer risk: 

Weight loss decreases infiltrating macrophages in adipose tissue inflammation, systemic complications of proinflammatory adipokines, obesity-linked pathologies & delays carcinogenesis. Dietary restriction-motivated weight loss reduces colorectal inflammation, decreases rectosigmoid expression of multiple proinflammatory cytokines and markers of T -cell, macrophage accumulation & attenuates cancer 
pathways (FOS, JUN, STAT3, and NF-κB expression). 

Conclusion:

Visible weight loss reduces cancer risk, diminishes adipose-related inflammatory mechanisms, regulates tumour development & progression. Reduction and control of cancer risk demand a better understanding of cellular & molecular mechanisms behind obesity-induced inflammation, the proactive invention of early diagnosis biomarkers & accessible effective cancer therapy.

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