Decoding the Obesity Cancer Link
- Apr 14, 2025
- 3 min read
Written by Renee Hurley with Commentary by Dr. Kristy Brown
Obesity affects just about every system in the human body - due in part to chronic inflammation, hormone dysregulation and other factors - leading to subsequent conditions, such diabetes, kidney disease, and heart failure. Among the possible life-altering conditions is cancer. In fact, 40% of all cancers diagnosed in the United States each year are attributed or have some relation to obesity.1
Although, epidemiological data clearly shows the increase in cancer risk, more research is needed to better understand causation, the pathways attributing to the increased risks, and if and what can be done to reduce those risks in addition to weight loss. Currently, there are 123 active studies listed on ClinicalTrials.gov that are investigating the link between obesity and different types of cancer, including breast, ovarian, endometrial, prostate, rectal, gastrointestinal, pancreatic and liver. In addition, factors such as nutrition, physical activity, and mental health are being studied.2
To explore this further, we reached out to Dr. Kristy Brown to learn more about her research focus around the obesity-cancer link.
METABOLIC-PATHWAYS, ADIPOSE TISSUE AND CANCER
There is strong epidemiological data linking obesity to the development of at least 13 different cancers. Obesity-related liver cancer is unique among these as it occurs in a highly metabolic tissue that when dysfunctional, is associated with lipid accumulation in cells susceptible to tumorigenesis.
Other obesity-related cancers are supported by host metabolic dysfunction through systemic and microenvironment changes that drive tumor growth. Hyperinsulinemia and hyperglycemia, associated with diabetes and obesity, stimulate signaling pathways involved in regulating cell proliferation through protein synthesis, energy metabolism and various other pathways.
The adipose is also a major driver of cancer through the production of adipokines, like leptin, low-grade chronic inflammation and local biosynthesis of estrogens. These various factors have been shown to converge to stimulate the proliferation of cancer cells. The development of estrogen receptor positive breast and endometrial cancers with obesity, and occurrence after menopause when gonadal estrogen production has ceased, speak to the importance of adipose-derived steroid hormones.
How estrogen production is regulated in the adipose is a major focus of our research, and we have discovered the convergence of obesity-associated factors with dysregulated cell metabolism as major drivers of the adipose expression of aromatase, a key enzyme in the biosynthesis of estrogens and target of current endocrine therapy for the treatment of breast cancer.
Obesity is also associated with fibrosis in the microenvironment of many tumors that occurs as a result of tissue injury, including breast and liver. These changes in the extracellular matrix are associated with worse disease outcomes.
Our recent work also highlights a role for obesity to cause cancer, with poor metabolic health being associated with more damage to breast epithelium and fallopian tube (origin of ovarian cancer) DNA.
Given the important interaction between many obesity-associated factors, it is still not clear whether targeting one will be sufficient to prevent cancer development. The most effective approach will likely involve restoration of metabolic health through weight loss and exercise. In fact, exercise alone, independent of obesity, is associated with reduced risk of cancer.
It remains to be determined whether anti-obesity medications will be effective at reducing cancer risk, although recent data point significant benefit. How cessation of these medications and incorporation of healthy lifestyle affect risk and cancer-related outcomes is still unknown.
Written by Kristy A. Brown, PhD, Associate Professor of Metabolism and Cancer, Department of Cell Biology & Physiology, KUMC Co-Program Leader, Cancer Prevention and Control, University of Kansas Cancer Center
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