Larger Organs, More Cells – New Study Clarifies How Obesity May Increase Cancer Risk

Key Takeaways: 

• A new study suggests that larger organ size in people living with obesity increases cancer risk due to a higher number of cells
  
• Organ growth appears to be driven largely by an increase in cell number rather than simply larger cells
  
• Findings indicate that organ size may be a more precise predictor of cancer risk than BMI alone
  
  
  

A longstanding question in obesity and cancer

For many years, researchers have recognised a clear association between obesity and an increased risk of cancer, particularly in organs such as the liver, kidneys and pancreas. However, the biological mechanism underpinning this relationship has remained uncertain.

A research team from City of Hope and its Translational Genomics Research Institute, known as TGen, has now provided a clearer explanation. Their findings suggest that the relationship may be explained by a straightforward principle – larger bodies tend to have larger organs, and larger organs contain more cells.

This increase in cell number creates more opportunities for mutations and, consequently, cancer development.

Study design and key findings

The study, presented in Cancer Research, analysed data from 747 adults across a broad spectrum of body mass index (BMI), ranging from underweight at 18.5 kg/m² to severe obesity above 40 kg/m².

Researchers examined the pancreas, kidneys and liver, identifying a consistent pattern: as body weight increased, organ size increased proportionally.

For every 5-point rise in BMI:

• The liver increased in size by 12%
  
• The kidneys increased by 9%
  
• The pancreas increased by 7%
  

These findings demonstrate a measurable and progressive relationship between BMI and organ enlargement.

More cells, not just bigger cells

To better understand how organs grow, the research team analysed kidney tissue from autopsies and biopsy samples from living individuals. This allowed them to distinguish between two biological processes:

• Hypertrophy – where existing cells grow larger
  
• Hyperplasia – where the number of cells increases
  

First author Sophie Pénisson, PhD, explained the importance of this distinction:

“When an organ increases in size, the question is to know whether it’s because the cells in it become bigger or whether there are more of them [that are] the same size,” Pénisson said. “And the first case is we call hypertrophy, with bigger cells, and hyperplasia is when we have more cells.”

The results showed that approximately 60% of kidney growth was due to hyperplasia, meaning an increase in the number of cells, while the remainder was due to hypertrophy.

A simple but powerful explanation for cancer risk

These findings support the idea that a greater number of cells increases the likelihood of cancer simply by increasing the number of opportunities for mutations to occur.

Senior author Cristian Tomasetti, PhD, illustrated this concept with a simple analogy:

“Think of playing the lottery: The more tickets you buy, the greater your chances of winning,” Tomasetti said. “Similarly, the more cells in an organ, the more mutations and the greater the risk of one cell going awry during division and becoming cancerous.”

Importantly, this mechanism does not replace existing explanations such as inflammation or hormonal disruption. Instead, it works alongside them.

Pénisson elaborated on this interaction:

“If more cells is like having more raffle tickets, she said, ‘if on top of that, there is inflammation – it means you play more often. With greater frequency, again, you increase your risk of developing cancer.’”

Rethinking BMI as a predictor of risk

The study also raises important questions about the use of BMI as a measure of cancer risk.

Although BMI is widely used in clinical practice, the researchers observed considerable variation in organ size among individuals with similar BMI values. Some individuals within a “healthy” BMI range had organ sizes typically seen in severe obesity, while others with higher BMI did not.

The authors wrote:

“We…observe substantial interindividual variation in organ size among people with similar BMI: For example, some individuals in the healthy BMI range have organ sizes expected only in severe obesity, and vice versa. This large variability suggests that organ size itself may be a better predictor of cancer risk than BMI, a possibility we believe warrants further investigation.”

They further concluded:

“Taken together, these findings establish organ hyperplasia as a previously unrecognized contributor to obesity-related kidney, liver, and pancreatic cancer risk, complementing known mechanisms including inflammation, hormonal changes, and metabolic dysfunction.”

Pénisson reinforced this point:

“When an organ doubles in size, it is expected to roughly double its risk of developing cancer,” Pénisson said, noting that BMI does not distinguish between fat mass and lean tissue. “Our work suggests that, at least for some organs, their dimensions may predict cancer risk better than BMI.”

Can weight loss reverse the risk?

An important question arising from these findings is whether reducing body weight can reverse organ enlargement and lower cancer risk.

Tomasetti indicated that this is an active area of research:

“It’s actually something we are working on right now,” Tomasetti said. “But yes, preliminary data seem to indicate that essentially, you are reverting back according to the same process” that caused the weight gain.

He also referenced emerging evidence presented at the American Society of Clinical Oncology, suggesting a link between GLP-1 receptor agonists and reduced cancer risk, although further research is needed to confirm this relationship.

Implications for treatment and prevention

Given the global scale of obesity, affecting more than 2 billion people, these findings may have important implications for prevention strategies and treatment approaches.

Tomasetti suggested that therapies such as GLP-1 receptor agonists could play a broader role:

GLP-1 RAs “are something that should be given to people as a treatment option to reduce the cancer risk, among other things,” including heart disease.

While further research is needed, this study provides a clearer mechanistic link between obesity and cancer risk and highlights the potential importance of organ size as a clinical marker.