Research has uncovered that an increase in organ size from hyperplasia due to increased weight may increase the risk for several obesity-related cancers, according to findings published in Cancer Research.
“People have long been told that obesity increases cancer risk, but they are rarely told why. Our study reveals that excess weight doesn’t just affect metabolism or hormones—it can physically enlarge organs, creating more opportunities for cancer to take hold. Understanding that process matters because it helps explain how everyday health choices can shape cancer risk years for even decades down the line,” said senior author Cristian Tomasetti, PhD, Director of City of Hope’s Center for Cancer Prevention, Early Detection and Monitoring and Professor in the Early Detection and Prevention Division at TGen.
The study authors stressed that these findings highlight the importance of maintaining a healthy weight from early childhood to reduce cancer risk; they also believed that this association could be used to predict risk for obesity-related cancers more accurately than body mass index (BMI).
Background and Study Methods
The underlying mechanisms for why obesity is a risk factor for several cancers is as yet unknown. Researchers believed that a possible mechanism is the growth of organs to match metabolic needs, thus raising the amount of cells that could become malignant.
They conducted a two-pronged study, first looking at the size of multiple organs in a cohort of 747 adults with varying BMIs. Next, the researchers explored enlarged organs in 25 individuals and quantified the cellular basis of the enlargement by looking at autopsy samples and biopsy data.
Key Findings
In the first part of the study, the researchers found that organs expanded as body weight increased. There was a 12% increase in the liver, a 9% increase in both kidneys, and a 7% increase in the pancreas size in line with every five-point increase in an individual's BMI.
In these individuals with organ enlargement, the total number of kidney cells had substantially increased. About 61% of the kidney enlargement was a result of hyperplasia, and the other 39% was due to hypertrophy.
Organ volume ratios were strongly correlated with cancer risk in the liver, kidneys, and pancreas, comparative to volumes of normal-weight adults. A doubling of the volume of an organ about equaled a doubling of the person's cancer risk in these three organs.
“When an organ doubles in size, it is expected to roughly double its risk of developing cancer,” said first author Sophie Pénisson, PhD, Associate Professor at TGen. “BMI is a poor proxy for telling us what the size of an organ is, as BMI doesn’t distinguish between fat and lean tissue. Our work suggests that, at least for some organs, their dimensions may predict cancer risk better than BMI.”
“Organs take time to grow, and it can take decades for cells to turn malignant,” explained Dr. Tomasetti. “Childhood obesity gives organ cells a longer runway to accumulate mutations and evolve into something worse.”
The study authors concluded that the link between obesity and cancer is likely due to increased metabolic demands from body size increases, expanding the organs through hyperplasia and resulting in more cells that are able to transform and become malignant.
“This exciting research deepens our understanding of how obesity may lead to cancer and highlights the role of organ growth in this process, which is also relevant for many individuals with diabetes. It will be important to see if the new anti-obesity drugs can revert this process for cancer prevention,” said Debbie C. Thurmond, PhD, of the Arthur Riggs Diabetes & Metabolism Research Institute and Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes at City of Hope.
The researchers plan to further explore if weight loss can reduce cancer risk and organ size, as well as the effects of GLP-1 drugs for weight loss on cancer risk.
DISCLOSURES: The study was supported by the John Templeton Foundation, the Lustgarten Foundation for Pancreatic Cancer Research, the Maryland Cigarette Restitution Fund, and the National Institutes of Health. Under a license agreement between Exact Sciences and the Johns Hopkins University, Dr. Tomasetti and the University are entitled to royalty distributions. Dr. Tomasetti is a paid consultant to Bayer AG, a member of the PrognomiQ Inc. scientific advisory board and the Founder of C2T Biosciences. For full disclosures of the other study authors, visit aacrjournals.org.
