Researchers at Winship Cancer Institute and their collaborators published a new scientific review in JAMA that examines how excess body fat may influence cancer development and what current evidence suggests about reducing risk.
Neil M. Iyengar, MD
A new scientific review published in JAMA examines how excess body fat may influence cancer development and what current evidence suggests about reducing risk.
The paper synthesizes findings from large population studies, clinical trials and laboratory research involving millions of patients worldwide. The authors report that overweight and obesity may contribute to roughly 10% of new cancer diagnoses each year in the United States.
The review was led by Neil M. Iyengar, MD, co-director of Breast Medical Oncology and director of Cancer Survivorship Services at Winship Cancer Institute of Emory University, along with collaborators from Memorial Sloan Kettering Cancer Center and University of Kansas Medical Center.
The review brings together existing evidence to explain how obesity affects the body in ways that may increase cancer risk and influence prevention strategies.
“The link between obesity and cancer is no longer theoretical, it is supported by extensive evidence across laboratory, human, and population studies,” says Iyengar. “Understanding these connections gives us a powerful opportunity to reduce cancer risk through targeted prevention, precision lifestyle change, and new medical approaches,” says Iyengar.
Understanding the biology behind obesity’s link to cancer
Obesity has long been associated with increased risk for several cancers, including colorectal, breast (postmenopausal) and endometrial cancers. The review explores the biologic mechanisms that may help explain this connection.
Excess fat tissue can trigger chronic inflammation, disrupt immune function and alter metabolic processes in ways that create a tumor-promoting environment in the body. Some research also suggests that obesity may contribute to DNA damage and genomic instability, which can increase the likelihood that cancer develops.
“Fat tissue is an important organ that maintains the balance of many bodily functions, but too much body fat changes these functions at a fundamental level,” Iyengar says. “It can drive chronic inflammation, alter hormone and metabolic signals, and interfere with the body’s natural defenses against cancer. Together, these changes can create conditions that allow tumors to form and grow,” Iyengar says.
By examining these mechanisms, researchers hope to better understand why obesity is linked to cancer risk and how prevention strategies might address these biological pathways.
What weight loss may mean for cancer prevention
The review also evaluates research on whether weight loss can reduce cancer risk.
Some studies suggest that modest weight loss may not significantly change cancer risk. Larger reductions in body weight, greater than about 10%, may be needed to meaningfully reduce some of the biologic effects associated with obesity.
Researchers also examined emerging evidence on weight-loss treatments, including bariatric surgery and newer medications such as GLP-1 receptor agonists. Early studies suggest these approaches may be associated with lower rates of certain obesity-related cancers, though longer-term research is needed.
“Avoiding obesity and maintaining healthy body composition are important pieces of cancer prevention. If obesity develops despite these intentions, recent research indicates that substantial amounts of weight loss may be required to truly shift the biology associated with cancer risk,” Iyengar says. “The encouraging news is that we now have a better understanding of many tools, such as personalized lifestyle interventions, medications, and even surgery, that can help patients achieve and sustain optimal metabolic health,” Iyengar says.
Implications for cancer care and survivorship
For clinicians and researchers, understanding how obesity influences cancer development may help inform both prevention and survivorship care.
Iyengar’s research focuses on the relationship between metabolism, inflammation and cancer outcomes, including how lifestyle and metabolic factors affect patients during and after cancer treatment.
As director of Cancer Survivorship Services at Winship Cancer Institute, he says these findings highlight the importance of addressing metabolic health as part of long-term cancer prevention and care.
“Cancer risk reduction and survivorship care extend beyond treating tumors alone,” Iyengar says. “Effective cancer prevention and treatment plans must include strategies to optimize metabolic health through personalized lifestyle interventions and anti-obesity treatments.” Researchers say additional studies will be needed to better understand how weight loss, metabolic therapies and other interventions may reduce cancer risk over time.
This work was supported in part by grants from the National Institutes of Health and the National Cancer Institute, along with support from the Breast Cancer Research Foundation, American Institute for Cancer Research, American Cancer Society and other foundations. Full funding details and disclosures are available in the published article.
Obesity-Related Cancer, A JAMA Podcast
Iyengar discusses the biological pathways that may promote cancer in people with overweight or obesity and potential therapies with JAMA Deputy Editor Mary McDermott, MD, in a JAMA Review in the Translational Science podcast.