GI Cancer and Obesity: Fighting One Means Addressing the Other

By 2030, it is projected that most Americans will be overweight, and of those, nearly 50% of adults will be obese. Although the majority of Americans are aware that obesity can have adverse health consequences, survey findings show that few are aware that it can increase cancer risk.

The link between weight and cancer may not be linear, yet large-scale epidemiologic studies have demonstrated a consistent and compelling association between the risk for cancer development and obesity, as defined by body mass index (BMI).

Studies also show that obesity decreases lifespan by up to 8 years and is linked to at least 236 other medical problems, including 13 types of cancer (Table).

Table. Cancers Related to Obesity

Gastrointestinal (GI) Cancers	Other Cancers
Esophageal adenocarcinoma	Breast (menopausal women)
Colon and rectal	Uterine
Gallbladder	Renal
Gastric	Ovarian
Liver	Thyroid
Pancreatic	Meningioma
	Multiple myeloma

The complex manner in which obesity drives cancer risk was previously highlighted in a review. The authors noted that chronic inflammation is a characteristic of obesity and a known mediator of cancer. Obesity-induced inflammation adds additional cancer risk via multiple mechanisms of adipose dysfunction and increased proinflammatory factors. Dysregulation of leptin, adiponectin, and chemokines results in cancer microenvironment changes to enhance protumoral consequences. Additionally, insulin resistance, hyperglycemia, and dyslipidemia resulting from obesity can impact tumor growth and development.

Obesity and GI Cancers

GI cancers account for 26% of the global cancer incidence and 35% of all cancer-related deaths. Systemic literature reviews have revealed a strong causal association between obesity and esophagus, liver, colon, gastric cardia, and pancreas cancers.

The International Agency for Research on Cancer reported an increased relative risk of 1.5 to 1.8 for GI cancers with a BMI ≥ 40, as compared with a normal BMI. In addition, patients with colon cancer and pancreatic cancer have poorer survival rates if overweight or obese at the time of diagnosis. This can be attributed to the increased risk for cancer recurrence, higher incidence of cancer-related mortality, and decreased effective delivery of systemic cancer therapy for individuals with obesity.

Obesity is the most common risk factor for nonalcoholic fatty liver disease (NAFLD). Recent studies showed that NAFLD was associated with an increased incidence of multiple cancers, especially hepatocellular carcinoma (HCC). NAFLD is also correlated with an increased rate of extrahepatic cancers like pancreatic cancer, kidney/bladder cancer, and melanoma.

In a meta-analysis, the prevalence of HCC in noncirrhotic nonalcoholic steatohepatitis (NASH) was as high as 38% in patients with obesity. Recent research showed that obesity causes oxidative stress that triggers the STAT-3 signaling promoting HCC independently of NASH, which itself results from STAT-1 signaling.

Additional Impacts

Obesity can affect long-term functional status, which may impact decision-making related to cancer management.

Metabolically healthy obese adults age faster than normal-weight adults with similar health. They also have a greater incidence of mobility limitation and disability in older age from the decline in physical function and worsening of body pain.

Globally, excess body weight is the third most common attributable risk factor for cancer behind smoking and infection, and second to smoking in Western populations.

Strategies for Reducing Obesity and Its Associated Cancer Risk

Although no obesity-specific marker has been identified for us to target, and we lack randomized data on interventions, there is a significant amount of observational evidence that weight loss in obesity reduces cancer risk overall.

The Swedish Obese Subjects Study revealed fewer overall cancer diagnoses for patients with obesity who received bariatric surgery when compared with standard care without intervention. Another study from the United States concluded that bariatric surgery for patients with obesity reduced the risk for all cancers, including obesity-related cancers. Specifically for GI cancer, bariatric surgery was associated with reduced colon cancer and pancreatic cancer.

Cancer risk reduction can be achieved without bariatric surgery.

Exercise can prevent or inhibit numerous disease conditions, including cancer.

Higher adherence to the Mediterranean diet is associated with a lower risk for cancer mortality and the risk of developing cancer, including colorectal cancer, gastric cancer, and liver cancer. The beneficial effects of the Mediterranean diet are mainly driven by higher intake of fruits, vegetables, and whole grains. For HCC, the intake of coffee, tea, and fish, along with healthy dietary patterns, may decrease the risk.

Although a renewed focus on reducing obesity in our patients is surely warranted, it is not the only means we have for managing this condition. Reducing consumption of tobacco and alcohol, immunizing against hepatitis B virus infection, and screening for colorectal cancer are other preventive measures that are also important for controlling GI malignancies.

Vicki Shah PA-C, DMSc, MMS, is the Solid Organ Transplant Lead Advanced Practice Provider at Rush University Medical Center in Chicago. She has an obesity medicine certificate from the Obesity Medicine Association with a successful weight intervention clinic in liver disease. She is a national speaker for continuing medical educational conferences with the Chronic Liver Disease Foundation. She serves on the editorial board for Clinical Liver Disease, a multimedia review journal, as well as educational chair for the AASLD Associates special interest group and member for AASLD NASH special interest group. She continues to have an active role in the American Liver Foundation as a Great Lakes board member and Medical Advisory Committee member.

Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the AASLD and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.

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