Obesity, Weight Change, and Colorectal Cancer Risk

A person’s risk of developing colorectal cancer is impacted by many different factors, including age, personal family history, genetics and other medical conditions such as inflammatory bowel disease.

Colorectal cancer is also associated with a wide variety of lifestyle-related risk factors, including:

• A diet high in fat, red and processed meats
• A diet low in fruits, vegetables and fiber
• Excessive alcohol consumption
• Tobacco use
• Leading an inactive or sedentary lifestyle

Among these risk factors, obesity has arguably become one of the most prevalent risk factors, due to its high prevalence in the US. A recent report by the National Health and Nutrition Examination Survey (NHANES) has reported a 40.3% prevalence rate of obesity in adults, with older adults being more likely to be obese. Meanwhile, severe obesity was reported in 9.4% of adults, with an increasing trend from 2021 to 2023.

Obesity is prevalent even in children aged 2-19, with 19.2% of them being obese, and 6.1% being severely obese from the survey's findings in 2018. While children may be less obese than their adult counterparts, different cohort studies have shown that 55% of obese children remain obese in adolescence, and 80% of obese adolescents continue to be obese into adulthood, with 70% of them being obese over the age of 30.

These striking figures are cause for alarm, with many health organizations, such as the World Health Federation and the World Obesity Federation, calling it a public health crisis. However, how exactly do we measure obesity?

Weight is often used as a defining characteristic of obesity, and the body mass index, or BMI, is a commonly used metric to measure obesity.

BMI is based on a person’s weight in kilograms and their height in meters, and can be calculated using the following formula:

A person’s weight classification can then be determined based on the following BMI ranges:

• Below 18.5: Underweight
• 18.5 to 24.9: Normal
• 25.0 to 29.9: Overweight
• 30.0 to 39.9: Obese
• 40 and above: Severely obese

Despite the widespread use of BMI as a metric for obesity, it has been argued that the index does not accurately capture the body fat count of an individual, as it does not take into consideration other factors that contribute to weight, including muscle mass, bone density, overall body composition, and demographic differences such as race and sex.

Researchers have argued that abdominal or visceral fat, and by extension waist circumference may be a more accurate indicator of obesity and opt to use other ratios such as waist-to-hip ratio or waist-to-height ratio to measure obesity concurrently with BMI.

The increased risk of colorectal cancer as a result of obesity is already well established in medical literature. A review of epidemiological studies found obese men particularly vulnerable, with obesity contributing a 30–70% increased risk of colorectal cancer, though the association is not well linked for women.

While obesity as a risk factor for colorectal cancer is well-documented, the exact physiological pathways that result in cancerous growth is still up for debate. Of the potential culprits, obesity-induced inflammation is one of the more frequently studied causes.

More specifically, diet-induced obesity results in the enlargement of white adipose tissue, the predominant type of fat found in the human body and in visceral fat. The enlargement causes the release of free fatty acids as well as inflammatory cytokines like tumor necrosis factor alpha (TNFα). Diet-induced obesity results in these cytokines being overexpressed in the colon epithelium, where elevated levels of TNFα result in alterations in the Wnt signaling pathway that changes the genetic makeup of colon epithelial cells such that they progressively grow into tumors.

An indirect but nonetheless related mechanism pertains to the elevated levels of insulin and insulin-like growth factor 1 (IGF-1), which usually precedes the development of type 2 diabetes, another colorectal cancer risk factor. Besides regulating the body’s metabolism, insulin has been found to also stimulate growth of colon lining and cancer cells in vitro. Additionally, these cancer cells express IGF-1 receptors; colon cancer cells in particular express higher levels of insulin-binding receptors compared to normal epithelial cells.

Compared to the effects of weight gain on the risk of colorectal cancer, fewer studies have been done to assess if weight loss in obese individuals changes that risk.

One recently published study conducted over a seven-year period found that while weight gain in adulthood increased the chances of developing adenoma (non-cancerous tumors), weight loss in adults was also associated with a 46% reduced risk of non-cancerous tumor formation. Again, the associated risk and subsequent change were stronger in men than in women.

Kathryn Hughes Barry, MD, Department of Epidemiology and Public Health, University of Maryland School of Medicine, and senior author of this study, said, “Our findings suggest that avoiding weight gain in adulthood may help lower someone’s chance of developing a pre-cancerous growth called colorectal adenoma, which may, in turn, reduce the risk of developing colorectal cancer”.

While this study presents a potential solution to not only reducing the risk of colorectal cancer but numerous other obesity-related diseases, implementation may not be as straightforward.

Conversation about obesity is not aided by decades of stigmatization against hefty individuals who are often blamed for their weight and size despite medical and hereditary conditions that can result in obesity.

Much of the stigmatization, or ‘fat-shaming’ is often disguised as attempts to motivate these individuals towards a healthier lifestyle, particularly promoting weight loss either through diet or lifestyle changes. While many will claim to do it in good faith, studies have found it counterproductive to shame a person into action of reform, suggesting that such behavior can result in the opposite: binge eating disorders that lead to more weight gain.

On the flip side, the now-mainstream social movement advocating body positivity — originally meant to promote acceptance of different body types — is often misconstrued or interpreted as promoting obesity and obstructing health initiatives to reduce a major risk for many high-mortality diseases.

While evidence of the detriment that obesity has on health and quality of life continues to stack, the important discussion pertaining to individual health and obesity continues to be, perhaps ironically, the elephant in the room.