Obesity and Cancer: Existing and New Hypotheses for a Causal Connection

Abstract

Existing explanations of obesity-associated cancer emphasise direct mutagenic effects of dietary components or hormonal imbalance. Some of these hypotheses are reviewed briefly, but recent evidence suggests a major role for chronic inflammation in cancer risk, possibly involving dietary content. These ideas include the inflammation-induced activation of the kynurenine pathway and its role in feeding and metabolism by activation of the aryl hydrocarbon receptor (AHR) and by modulating synaptic transmission in the brain. Evidence for a role of the kynurenine pathway in carcinogenesis then provides a potentially major link between obesity and cancer. A second new hypothesis is based on evidence that serine proteases can deplete cells of the tumour suppressors Deleted in Colorectal Cancer (DCC) and neogenin. These enzymes include mammalian chymotryptic proteases released by pro-inflammatory neutrophils and macrophages. Blood levels of chymotrypsin itself increase in parallel with food intake. The mechanistically similar bacterial enzyme subtilisin is widespread in the environment, animal probiotics, meat processing and cleaning products. Simple public health schemes in these areas, with selective serine protease inhibitors and AHR antagonists and could prevent a range of intestinal and other cancers.

Contributions of innate type 2 inflammation to adipose function

“…The most recent data reports ~70% of the American population is overweight (body mass index (BMI) ≥ 25 kg/m 2 ) and ~35% is obese (BMI ≥30 kg/m 2 ) [2,3]. The need to reduce obesity stems from the increased risk of comorbidities such as cardiovascular disease, type 2 diabetes, asthma, certain cancers, and various other diseases [4][5][6]. A report compiled of 57 prospective analyses of nearly a million adults, showed that obesity can decrease a person's life span up to 10 years [7].…”

Obesity-induced reduction of adipose eosinophils is reversed with low-calorie dietary intervention

“…; Khalid and Holguin ; Stone et al. ). Indeed, a report of 57 prospective analyses comprised of nearly a million adults, showed that obesity can decrease a person's life span by up to 10 years (Prospective Studies et al.…”

“…Obesity has been one of the fastest growing factors negatively influencing human health over the last several decades (Flegal et al 2012;Ogden et al 2015;CDC, 2016). In particular, obesity increases the risk for type 2 diabetes, insulin resistance, cardiovascular disease, certain cancers, infertility, asthma, and many other diseases (Shoelson et al 2007; Khalid and Holguin 2018;Stone et al 2018). Indeed, a report of 57 prospective analyses comprised of nearly a million adults, showed that obesity can decrease a person's life span by up to 10 years (Prospective Studies et al 2009).…”

HIV‐1, HAART and cancer: A complex relationship

“…This cannot be solely explained by targeted cancer screening for these types of cancer (mammography, colon/sigmoidoscopy, PSA test) or hormone levels alteration due to HIV infection . Overweight/obesity is less prevalent in people living with HIV than in general population, and that is a proposed risk factor for gastrointestinal tract tumors, breast, endometrial and renal cancers . This requires further investigation with a direct comparison of HIV‐infected people with body mass index‐matched uninfected people.…”

“…42 Overweight/obesity is less prevalent in people living with HIV than in general population, and that is a proposed risk factor for gastrointestinal tract tumors, breast, endometrial and renal cancers. 13,43 This requires further investigation with a direct comparison of HIV-infected people with body mass index-matched uninfected people. These trends may also be due to viral-host interaction.…”