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Clinicalworldwide, the Prevalence of Both Obesity and Cancer Are Rising

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Clinicalworldwide, the Prevalence of Both Obesity and Cancer Are Rising J R Coll Physicians Edinb 2020; 50: 392–7 | doi: 10.4997/JRCPE.2020.408 REVIEW Obesity and the Risk of Malignancy: An Evolving Saga Sophie Wilcock1, Nadim Haboubi2 ClinicalWorldwide, the prevalence of both obesity and cancer are rising. So far, Correspondence to: there is an association between obesity and an increased risk of at least Professor Nadim Haboubi Abstract 20 different cancers and this number is increasing. The mechanism behind Department of Clinical obesity increasing the risk of cancer varies. The importance of looking at all Nutrition and Obesity aspects of obesity, such as hip to waist ratio, body fat distribution and waist University of South Wales circumference, in addition to BMI has been acknowledged in order to further Pontypridd understand these mechanisms. The duration of time a person is obese for, and whether their UK weight gain was in childhood or adulthood can also affect risk of cancer, however this can be hard to distinguish as obese children and adolescents frequently remain obese into adulthood. Email: [email protected]. Keywords: Obesity, cancer, carcinoma, BMI, oncology, malignancy, fat uk Financial and Competing Interests: No confl ict of interests declared Introduction other cancers (Table 1), including more recently advanced prostate cancer, have also been found to be increased with The World Health Organisation (WHO) have recognised obesity.9,10,11,12 obesity, defi ned as a body mass index (BMI) ≥ 30kg/m2, as a widespread epidemic and a disease within itself, which is In this narrative review we have looked at current epidemiology chronic and progressive in nature with potential for relapse.1,2 for both obesity and cancer and we have appraised the In 2016 an excess of 1.9 billion individuals aged 18 plus current understanding of how obesity can increase the risk were overweight (with a BMI of ≥25kg/m2), of which more of certain cancers. In doing so, we have primarily focused than 650 million had a BMI ≥ 30kg/m2. World-wide rates of on how body fat distribution and the duration and onset of obesity have increased almost three fold between 1975 and obesity can possibly affect the cancer risk. 2016.2 If this trend is to continue, it is predicted that between 2016 and 2025, worldwide obesity levels will increase from Search Strategy 11% to 18% in men and from 15% to exceed 21% in women.2,3 We collated and compared the relevant literature for papers Being overweight or obese and having an excess adiposity published in English between 1997 and 2020, searched is known to increase the risk of many diseases, including using PubMed. Key words used in the search include, but several cancers. In the ‘Father of Medicine’, Hippocrates are not limited to, ‘cancer’, ‘obesity’, ‘oncology’, ‘BMI’ and depicted cancer as a crab like structure, and highlighted ‘malignancy’, whilst key terms included ‘body fat distribution’ the risks associated with excessive food consumption.4 An and ‘onset of obesity’. Some papers were identifi ed from observational UK based study which involved 3.6 million the reference lists of articles found in the initial search. No people, demonstrated that both cardiovascular disease study was excluded, whilst studies with a long follow up time and cancer are signifi cant causes of mortality in those who were favoured. are overweight or obese.5 Additionally, obesity is one of the biggest preventable causes of cancer in the UK, second only Incidence of Obesity and Cancer with to smoking.6 Associated Mortality Adequate evidence has become available to support the Cancer in itself is one of the primary causes of death across association between excess body fat and the development the globe causing 9.56 million deaths worldwide in 2017, of 14 different cancers.7 These include, but are not limited second only to cardiovascular diseases, which obesity also to, some of the most common cancers, such as breast increases the risk of.13 Published work identifi ed that in the and colorectal, as well as some of those with the poorest same year, obesity led to 4.7 million premature deaths.14 prognoses, such as oesophageal and pancreatic.7,8 Risk of Trends have shown that the number of obese and overweight 14th year Medical Student, Cardiff University School of Medicine, Cardiff, UK; 2Professor, Department of Clinical Nutrition and Obesity, University of South Wales, Pontypridd, UK 392 JOURNAL OF THE ROYAL COLLEGE OF PHYSICIANS OF EDINBURGH VOLUME 50 ISSUE 4 DECEMBER 2020 Obesity and malignancy Table 1 Cancers linked with obesity *Breast cancer *Oesophageal *Kidney (Renal cell *Colon *Thyroid (post-menopausal) (adenocarcinoma) carcinoma) *Liver *Rectum *Pancreatic *Gall bladder *Multiple myeloma *Gastric cardia *Ovarian *Endometrium *Meningioma Leukemia Non-Hodgkin’s Prostate Cervical Glioma Malignant melanoma lymphoma *Those recognized by the International Agency for Research on Cancer (IARC) adults in the world, and in the UK are increasing annually as and obese individuals who currently have cancer were found are the number of individuals with cancer.13,15 to have worse survival rates, and those who have had it previously, were found to have a greater risk of recurrence for The number of individuals dying from cancer worldwide is multiple cancers including colorectal and breast.3 Collectively, increasing. Approximately 5.7 million people worldwide died this highlights the rationale behind this literature review. as a result of cancer in 1990 and by 2017 there had been almost a 68% increase, however this is not taking population How Obesity Can Increase the Risk of expansion into account. When population growth is taken into Cancer – What we know so far account, there has still been a 17% increase in deaths due to cancer, which is shown as death rate (deaths per 100,000). The relationship between obesity and cancer is not fully When looking at the UK in isolation, from the 1.7 million understood, whilst the exact mechanisms of carcinogenesis deaths in 1990, there was a general reduction in death rates will vary between cancers, alluding to the complexities of the from cancer up until the year 2014, but there has been a relationship.3 In some cases, it is the direct effect of having steady increase since then.13 excessive adipose tissue that will increase risk, as having more adipose tissue can enhance the metabolism of sex Extremes of BMI have been associated with an increase in hormones. This is particularly relevant to hormone sensitive overall mortality risk, which increases exponentially when BMI cancers, including those of the breast, endometrium and is greater than or equal to 30 kg/m2. Furthermore, overweight prostate.3,16 Figure 1 Hyperinsulinemia and cancer risk IGFBP-1 = insulin like growth factor binding protein 1; IGF- 1 = insulin like growth factor 1; SHBG = sex hormone binding globulin DECEMBER 2020 VOLUME 50 ISSUE 4 JOURNAL OF THE ROYAL COLLEGE OF PHYSICIANS OF EDINBURGH 393 S Wilcock, N Haboubi Figure 2 Biochemical pathways linking obesity to cancer IL6 = interleukin 6; IL8 = interleukin 8; MCP-1 = monocyte chemoattractant protein -1; MIP 1α/ 2α = macrophage inflammatory protein 1 alpha/ 2 alpha; TNFα = tumour necrosis factor alpha In other cases, the risk is increased secondary to the diseases Leptin, visfatin, adiponectin and resistin are adipokines that can result from obesity, such as type 2 diabetes mellitus released from adipocytes.24 Biochemical pathways resulting (T2DM), which has been shown to increase the likelihood of from excess adiposity has been postulated as another certain cancers.3,7 Aside from its role in energy metabolism, mechanism which relates cancer to obesity. In obese insulin has mitogenic properties meaning it can induce cell individuals, the levels of pro-infl ammatory adipokines are division.17 This is apparent in obesity, when the number of elevated, whilst the levels of anti-infl ammatory adipokines are pancreatic beta cells increases to produce more insulin to reduced. In addition, there are altered levels of chemokines overcome insulin insensitivity (a consequence of obesity). and cytokines.24,25 Collectively this resultant infl ammatory This results in chronic hyperinsulinemia, the effects of which environment promotes carcinogenesis as shown in Figure 2. can be seen in Figure 1. Some of the physical medical problems that result from Colorectal cancer is amongst the top three causes of obesity can also raise the likelihood of cancer. Gastro- cancer deaths and evidence suggests hyperinsulinemia is oesophageal refl ux disease (GORD) is more prevalent in a key mechanism for its development. Individuals who are obese individuals. Erosive oesophagitis as well as Barrett’s obese have a 30% higher risk of developing colorectal cancer oesophagus (BO) could complicate GORD and increase the compared to those who’s BMI is less than 30 kg/m2. 18,19 risk of adenocarcinoma of the oesophagus.8 Genetics also play a role. The fat mass and obesity Oesophageal adenocarcinoma that results from BO is associated (FTO) gene plays a role in appetite control and considered a male predominant disease, with males at whilst overexpression of this gene is linked with increased least four times more likely than their female counterparts food uptake, there is evidence to suggest there is a high risk to develop it.26 Oestrogen receptors have been demonstrated variant of this gene that increases risk of obesity, but the in Barrett’s mucosa, with certain subtypes deemed more gene has also been linked directly to breast, endometrial, protective than others.27,28 Furthermore, studies
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