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Evidence-Based Oncology October 2019

Obesity and Cancer Risk: A Public Health Crisis

Alexander J. Alvarnas; and Joseph C. Alvarnas, MD
Obesity is associated with a number of adverse health-related complications and carries an elevated individual all-cause mortality risk. It would be hard to overstate the increased adverse health outcomes for obese individuals. What is far less well recognized by the general public is the significant link between obesity and increased cancer risk.
Obesity is becoming an increasingly common health condition in the United States and other Western nations. This condition is defined as an individual having a body mass index (BMI) of 30 kg/m2 or greater.1 Although some data suggest that other measures of obesity, such as percentage of body fat or fat mass index, might be better predictors of obesity-related complications such as metabolic syndrome, BMI is still the most commonly used metric to estimate individual obesity.A BMI greater than 40 kg/m2 indicates extreme obesity.3

The United States has the highest obesity rates in the world.4 According to a JAMA paper published in 2016 based on data from 26,468 participants from 2 previous National Health and Nutritional Examiner Survey (NHANES) trials, the crude rate of obesity for data year 2013 was 35.2% for men and 40.5% for women. The overall age-adjusted obesity rate was 37.7%. The prevalence of class 3 obesity (BMI >40 kg/m2) was 5.5% for men and 9.9% for women.5 When comparing obesity rates in 2015 with those of the 1980s, one study found that average body weight had increased by 10%.6 By comparison, in 1990, the US obesity rate of obesity was just 15%.

Risk factors for obesity vary by age. For children younger than 11 years, screen time/hours per day of media exposure is a statistically significant risk factor. For individuals 12 years and older, risk factors include consumption of fast-food meals, lack of physical exercise, spending more than 8 hours daily engaged in sedentary activity, and female gender.4 Race, income level, education levels, and geographic location within the United States are all associated with obesity risk. The large states of the South and Midwest have the highest levels of adult obesity, with rates of 32.4% and 32.3%, respectively, whereas states located in the West and Northeast have the lowest obesity rates, 26.1% and 27.7%, respectively.7

Children living with a parent without a high school degree had an obesity rate 3 times higher than those living with parents who had obtained a higher degree of education. As noted above, disparities continue along racial lines, as well, with Asian Americans adults having the lowest rate of obesity (12.7%), followed by non-Hispanic white adults (37.9%), African American adults (46.8%), and Hispanic adults (47%).8

Obesity is associated with a number of adverse health-related complications and carries an elevated individual all-cause mortality risk.9,10 It would be hard to overstate the increased adverse health outcomes for obese individuals. In one study, the risk of type 2 diabetes (T2D) for individuals with a BMI >30 kg/mwas 28 times higher than it was for individuals of normal weight; for those with a BMI >35 kg/m2, the risk rose to 98 times higher.11 The authors of the study noted, “The national prevalence rates of diabetes have increased in parallel with the rates of obesity.”10

Obesity also carries a markedly elevated risk of other chronic health conditions, including hypertension, hyperlipidemia, coronary artery disease, congestive heart failure, and stroke.Beyond the direct health implications of the obesity epidemic, the worldwide economic burden related to obesity is estimated to be nearly $2 trillion.9 The authors of a 2009 Health Affairs paper on the escalating economic impact of obesity in the United States said, “Our overall estimates show that the annual medical burden of obesity has risen to almost 10% of all medical spending and could amount to $147 billion per year in 2008.”12 Current estimates of our current national health care costs related to obesity are as high as $210 billion.8

What is far less well recognized by the general public is the significant link between obesity and increased cancer risk. Data from the United Kingdom indicate that, in the next 15 years, obesity may overtake smoking as a leading cause of preventable cases of cancer.13 Population-based data from 10,038,812 patients enrolled in the UK Clinical Practice Research Datalink were analyzed for a statistical evaluation of the relationship between 24 cancer types and an overweight or obese level BMI.14 This study demonstrated a statistically significant association between obesity and 13 cancer types, including cancers of the breast, ovary, uterus, cervical, ovary, renal, gallbladder, liver, colon, and thyroid and acute leukemias. The relationship between BMI and several cancer types was linear.14 In an accompanying editorial, the authors noted:

Each 5 kg/m2 increase in BMI was associated with higher risks of cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56–1·69), gallbladder (1.31, 1·12–1.52), kidney (1.25, 1.17–1.33), liver (1.19, 1.12–1.27), colon (1.10, 1.07–1.13), cervix (1.10, 1.03–1.17), thyroid (1.09, 1.00–1.19), ovary (1.09, 1·.04–1.14), postmenopausal breast (1.05, 1.03–1.07), pancreas (1.05, 1.00–1.10), and rectum (1.04, 1.00–1.08), and of leukemia (1.09, 1.05–1.13).15

In addition, there are data demonstrating a less pronounced but statistically significantly increased risk of multiple myeloma, meningioma, esophageal, and pancreatic cancers.16-19 Numerous studies from the United States also demonstrate that obesity has become a leading preventable cause of cancer. Data from the American Cancer Society demonstrate that obesity is responsible for about 8% of all cancers in the United States and about 7% of all cancer deaths.20

The mechanisms through which obesity leads to an increased risk of cancer are multiple and highly complex. They reflect the sometimes synergistic impact of altered hormone and cytokine secretion, changes to the tumor microenvironment, and intracellular alterations to regulatory proteins. The biological activity of adipose tissue is enormously complex. Authors of one study note that, “In obese patients, excessive accumulation of adipose tissue leads to elevated levels of circulating free fatty acids and increased expression of serum adipokines, such as leptin, visfatin, and cytokines…”21 As such, obesity creates a pro-inflammatory state. The obesity associated pro-inflammatory state results in the elevation elaboration of cytokines, such interleuken-6 (IL-6) and tumor necrosis factor α (TNFα), which are elaborated at higher levels than in individuals who are not obese. This chronic inflammatory state results in changes to both the cellular microenvironment and to numerous intracellular molecular pathways.21-23

While the precise cellular and molecular biological changes underlying obesity-related cancer may vary considerably between patients, recent research highlights some of the key mechanisms through which obesity may promote tumorigenesis. For men with high fat diets and prostate cancer, murine models demonstrate that a high fat diet alters phosphorylation of the signal transducer and activator of transcription-3 (STAT3) regulatory protein and palmitic acid levels in tumor cells.22 For women with endometrial cancer, the presence of obesity and metabolic syndrome likely increase cancer risk through a variety of mechanisms. Increased estrogen levels produced by the effects of both hyperinsulinemia and an increase in adipocyte-derived estrogen likely play a role. In addition, increased activity of rapamycin (mTOR)/vascular endothelial growth factor (VEGF) and changes to the tumor microenvironment mediated by cancer-related fibroblasts also play a role. In addition, adipose tissue-related proinflammatory cytokines such as IL-6 and TNFa likely play a role in tumorigenesis.21

Given the concerning increase in the prevalence of obesity and the frightening growth rate of obesity-related cancers, solutions have thus far proven elusive. Just as obesity-related cancer risk is projected to overtake smoking-related cancer risk as the leading preventable set of cancers, the success of the nation’s long-term smoking cessation efforts provide an evidence-based perspective on a potential path forward toward mitigating the risk of obesity-related cancer.24 Indeed, just as data demonstrate that smoking cessation reduces cancer risk, there is also an evolving body of data that demonstrate that reducing individual obesity may produce a commensurate fall in cancer risk rates. In one trial, investigators found that, “a history of bariatric surgery and maintained normal weight after surgery is associated with a 71% and 81% reduced risk for uterine malignant tumors.”25

The increased prevalence of obesity reflects the impact of both individual behavior and the massive societal changes of the past 5 decades that have contributed to this phenomenon. This includes the proliferation of calorie-rich inexpensive fast foods, a shift toward increasingly sedentary forms of work and recreation, and the presence of “food deserts” in many communities from the lower end of the socioeconomic spectrum.26 Efforts to reduce obesity rates are further hampered by an alarming lack of public awareness of the hazards of obesity. Data from the American Institute for Cancer Research demonstrate that only 50% of Americans are aware for the link between obesity and increased cancer risk.27 A study from the United Kingdom found that 75% of adults were not aware of the obesity-cancer link.13 Improving

public awareness is a first and essential step toward ensuring more effective cancer prevention efforts.

Beyond concerted efforts to cultivate a greater level of awareness regarding the hazards of obesity, there are both individually-targeted and broader social strategies for reducing obesity rates. Primary care physicians can and should play a central role in patient education and focusing upon risk reduction. This includes integration of obesity screening and discussions related to obesity risk reduction and management as part of routine clinic visits, beginning in childhood.28 Authors of a recent commentary in Family Medicine noted that, “A study in the United States suggested family physicians regularly failed to acknowledge weight problems in over half of consultations with adult patients who had a weight-related comorbid condition, yet when they did counsel them, patients were much more motivated to change health behaviors and have a greater awareness of health risks.”28,29 By focusing upon this issue when patients are young, physicians are more likely to foster better food and activity choices by their patients.

Copyright AJMC 2006-2020 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
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