Obesity’s Impact on Cancer Risk: How Organ Growth Through Hyperplasia Plays a Role
For years, the link between obesity and an increased risk of cancer has been well-established, but the underlying mechanisms have remained largely unclear. Novel research published in Cancer Research sheds light on this connection, identifying a process called hyperplasia – an increase in the number of cells in an organ – as a key driver. This growth, triggered by increased metabolic demands associated with higher weight, may create more opportunities for cancerous mutations to develop.
The Link Between Weight Gain and Organ Size
Researchers, led by 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, investigated the relationship between body mass index (BMI) and organ size in a cohort of 747 adults. The study revealed a strong positive correlation: as BMI increased, so did the size of the liver, kidneys, and pancreas. Specifically, a five-point increase in BMI was associated with a 12% increase in liver volume, a 9% increase in combined kidney volume, and a 7% increase in pancreas size.
Hyperplasia vs. Hypertrophy: The Cellular Basis of Organ Enlargement
To understand how organs enlarge, the researchers examined kidney cells from autopsy samples and biopsies. They found that approximately 61% of kidney enlargement was due to hyperplasia – an increase in cell number – while the remaining 39% was attributable to hypertrophy, an increase in cell size. This finding is significant because an increased number of cells inherently means more opportunities for genetic errors that can lead to malignant transformation.
Organ Volume and Cancer Risk: A Direct Correlation
The study further demonstrated a strong correlation between organ volume ratios (compared to normal-weight adults) and cancer risk across the liver, kidneys, and pancreas. A doubling in organ volume corresponded approximately to a doubling in cancer risk. “When an organ doubles in size, it is expected to roughly double its risk of developing cancer,” explained Sophie Pénisson, PhD, Associate Professor at TGen and first author of the study. “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.”
Implications for Cancer Prevention and Early Detection
These findings have important implications for cancer prevention strategies. The researchers emphasize the importance of maintaining a healthy weight from early childhood to reduce cancer risk, suggesting that early intervention could limit the “runway” for cells to accumulate mutations. “Organs seize time to grow, and it can take decades for cells to turn malignant,” Dr. Tomasetti noted. The study similarly suggests that organ size may be a more accurate predictor of obesity-related cancer risk than BMI alone.
Future Research and the Role of Anti-Obesity Drugs
Researchers are now exploring whether weight loss can reduce cancer risk and organ size, and investigating the potential effects of GLP-1 drugs – a newer class of medications used for weight loss – on cancer risk. 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, stated, “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.”
Key Takeaways
- Obesity is linked to increased cancer risk through a process called hyperplasia, where organs grow by increasing cell number.
- Organ size is strongly correlated with cancer risk, potentially offering a more accurate risk assessment than BMI.
- Maintaining a healthy weight, particularly from childhood, is crucial for reducing cancer risk.
- Further research is needed to determine if weight loss and anti-obesity drugs can reduce cancer risk by reversing organ enlargement.
Disclaimer: Dr. Tomasetti has financial ties to Bayer AG, PrognomiQ Inc., and C2T Biosciences, as well as a license agreement with Exact Sciences and Johns Hopkins University. For full disclosures, please visit aacrjournals.org.
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