*3.3.5 Obesity and cancer*

Different types of cancers associated with obesity include breast, endometrial, prostrate, pancreatic, adenocarcinoma of esophagus, colon cancer, meningioma, and cancers of ovary, kidney, thyroid, liver, etc. [92–94]. Though different mechanisms have been proposed, chronic inflammation is a major factor for cancer initiation and progression. Excess nutrients activate metabolic signaling pathways such as c-Jun N-terminal kinase (JNK), nuclear factor κ B (NFκB), and protein kinase R that may promote development of neoplasm [95, 96]. Synthesis of IGF-1 is stimulated by insulin. IGF-1 promotes tumor growth via the PI3K/Akt/mTOR and the Ras/Raf/ MAPK pathways [96]. IL-6, a pro-inflammatory cytokine produced during adipose tissue inflammation, activates the androgen receptor and promotes cell survival and proliferation in prostate cancer [97]. Aromatase, the rate-limiting enzyme of estrogen synthesis, is also stimulated by inflammatory cytokines and PGE2 [98–101].

Risk of gallstones is increased in obesity. Chronic gall bladder inflammation from gallstones may predispose to cancer of the gall bladder [102]. Similarly, chronic inflammation of hepatitis may increase the risk of liver cancer [103].

Cancer survivorship, including cancer progression, prognosis, recurrence, and quality of life are reported to be worsened by obesity [104, 105]. Obesity is associated with an increased risk of treatment-related lymphedema in breast cancer survivors and incontinence in prostate cancer survivors (treated with radial prostatectomy) [106, 107]. Risk of local recurrence was higher in obese/overweight male patients with stage II or stage III renal cancer [108]. Similarly, obesity increases the risk of mortality in patients with multiple myeloma [109].

### *3.3.6 Eye diseases associated with obesity*

Ocular manifestations of obesity are less known and not well documented. Its association with age-related cataract, glaucoma, age-related maculopathy, and diabetic retinopathy has been reported [110, 111]. Cortical and posterior subcapsular or PSC cataracts have been most consistently associated with obesity. Obesity-induced leptin resistance and hyperlipidemia promote formation of reactive oxygen species, which are involved in cataract formation. Other complications of obesity: insulin resistance, hyperglycemia, diabetes, diabetes, and hypertension (see above) are known to be risk factors for cataract.

Increased retroorbital adipose tissue seen in obesity has been reported to be associated with increased intraocular pressure (IOP) [112, 113]. Raised IOP may be a risk factor for glaucoma. The AREDS (Age-Related Eye Disease Study) Report [114] has reported an association between obesity and age-related macular degeneration. (AMD) Oxidative stress secondary to hyperleptinemia may cause damage to lipids in Bruch membrane and secretion of excessive vascular endothelial growth factor (VEGF), which elicit invasion of neovascularization in Bruch membrane in neovascular AMD [115]. Inflammation may also play a role in AMD development. Diabetic retinopathy, a common complication of T2DM (which is associated with diabetes), can result in loss of vision [116]. Other diseases of the eye that may be associated with obesity include retinal vein occlusion, oculomotor nerve palsy, recurrent lower eyelid entropion, keratoconus, papilledema, floppy eyelid syndrome and benign intracranial hypertension (pseudotumor cerebri) [117–121].
