The prevalence of obesity is continuing to rise, with an estimated increase of 0.5 units of body mass index (BMI) per decade during the last 3 decades.1 As a result, over 600 million adults across the world are obese, with a BMI of at least 30 kg/m2 or higher. In the United States, it is estimated that 69% of adults are overweight, with a BMI of at least 25 kg/m2, and 35% are obese, with a BMI of at least 30 kg/m2.2 Studies have estimated that 20% of cancer cases in Europe and North America can be attributed to obesity.2

The International Agency for Research on Cancer (IARC) has identified 13 sites of cancer in which there is sufficient evidence to suggest that reducing excess body corpulence would have a cancer preventive effect.3 These sites include malignancies of the esophagus, gastric cardia, colon or rectum, liver, gallbladder, pancreas, the postmenopausal breast, corpus uteri, ovary, renal cells of the kidney, meningioma, thyroid, and of the skin, such as melanoma. There was limited evidence linking adiposity to male breast cancer, fatal prostate cancer, or diffuse large B-cell lymphoma. There were determined to be inadequate data to link excess weight to cancers found in other locations.

There are multiple mechanisms that have been hypothesized to cause cancer among obese individuals, including differences in growth factors and sex hormones; elevated adipocytokine levels, which affect growth, immune, and tumor-regulatory functions; constitutive inflammation and oxidative stress; and an altered microbiome.4

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Cancer Risk

Meta-analyses of epidemiologic data suggest that obesity, defined as a BMI of at least 30 kg/m2 or 35 kg/m2 (depending on the study in question), is associated with an increased risk of developing multiple different cancer types. A meta-analysis of overall cancer incidence across 7 prospective cohort studies that included 43,419 individuals found that during a median follow-up of 12 years, per a standard deviation increase in each metric, the risk of cancer increased with hazard ratios (HR) of 1.11 (95% confidence interval [CI], 1.02-1.21) for BMI, 1.13 (95% CI, 1.04-1.23) for waist circumference (WC), 1.09 (95% CI, 0.98-1.21) for hip circumference (HC), and 1.15 (95% CI, 1.00-1.32) for waist-to-hip ratio (WHR).5 These data indicate a modest increase in the risk of obesity-related cancers — postmenopausal breast cancer, colorectal cancer (CRC), lower esophagus, stomach cardia, liver, gallbladder, pancreas, endometrium, ovary, and kidney cancers — with higher BMI or abdominal obesity. In addition, the study found that increases in BMI or adiposity also increased the risk of CRC.

Indeed, multiple meta-analyses provide evidence that suggests that being overweight or obese is associated with cancer risk. These cancers include digestive-tract malignancies, such as gastroesophageal, gastric, gallbladder, pancreatic, and colorectal cancers; cancers at reproductive sites, such as the breast, endometrium, ovaries, and prostate; as well as cancers of the lung; the brain (particularly meningiomas but also gliomas in women); and the thyroid.6-20 Across many  of the studies, cancer risk is also elevated in individuals who are deemed overweight; a person is typically considered to be overweight when the individual has a BMI of 25 kg/m2 to 29.9 kg/m2.

Not surprisingly, the duration of obesity also increases the risk of obesity-related cancers. For every 10 years of being overweight (having a BMI of 25 kg/m2 or higher), the risk of developing an obesity-related cancer was 36% (HR, 1.36; 95% CI, 1.12-1.60).2 A similar risk was observed for postmenopausal breast cancer and CRC.