Study Finds Mechanism Tying Obesity to Cancer Risk: Larger Organs With More Cells Raise the Odds

For years, scientists have known that obesity was linked to a higher risk of cancer, especially in certain organs. They just didn’t know precisely how it worked.

But now a team from City of Hope and its Translational Genomics Research Institute, or TGen, have uncovered the mechanism, which boils down to simple math: Bigger bodies have bigger organs, and bigger organs have more cells.

More cells, in turn, create more opportunities for cancer to occur, senior author Cristian Tomasetti, PhD, said in an interview with The American Journal of Managed Care^® (AJMC^®). Tomassetti is 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.

Published March 24, 2026, in Cancer Research, an official journal of the American Association of Cancer Research,¹ the study found a strong link between increased organ size and cancer risk, based on predictions and measurements of the pancreas, kidney, and liver among 747 adult patients.

The patients included those across a wide range of body mass indices (BMIs), from those very underweight at 18.5 kg/m² to those severely obese at more than 40 kg/m². Results showed that the organs grew larger as body weight increased. For every 5-point increase in BMI, the liver grew by 12%, the kidneys by 9%, and the pancreas by 7%.

The team then counted cells in samples of autopsied kidney tissue and reviewed the biopsy results from living patients. These data showed that 60% of kidney growth was due to an increase in the number of kidney cells, with the remaining 40% due to individual cells growing larger.

First author Sophie Pénisson, PhD, associate professor at TGen, said in an interview with AJMC that this is an essential question for which the answer has been unclear.

“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 finding provides evidence that increasing the number of cells is a major mechanism of tumorigenesis induced by obesity, alongside factors such as inflammation and hormonal imbalances. Tomassetti said this corrects earlier theories suggesting that larger organ size in obese people was caused by fatter cells—and it makes sense, because the more cells in an organ, the more opportunities there are for uncontrollable growth and malignancy.

“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 1 cell going awry during division and becoming cancerous.”

But what about other factors, such as inflammation? The mechanism of added cells works in tandem with these factors, Pénisson explained. 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.”

Both Tomasetti and Pénisson said their findings add fuel to the discussion that BMI is an imperfect measure of obesity and certainly of cancer risk. As a person gains significant weight, the size of organs can soar, even doubling, the study showed.

In their paper, 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.

“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,” they concluded.

“When an organ doubles in size, it is expected to roughly double its risk of developing cancer,” Pénisson said, 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.”²

So if increased organ size boosts cancer risk, does significant weight loss shrink organs—and thus reduce that risk?

“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 referenced a study presented last year at the American Society of Clinical Oncology Annual Meeting that found a link between GLP-1 receptor agonists (RAs) and reduced cancer risk, and said more work is needed in this area.³

Based on these latest findings, should there be more support for reimbursement for GLP-1 RAs if they not only aid weight loss but also possibly reduce cancer risk?

Tomasetti said there is a “pandemic” of overweight and obesity, numbering more than 2 billion people.⁴ Given that, 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.

References

1. Pénisson S, Weischer M, Li L, et al. Hyperplasia functions as a link between obesity and cancer. Cancer Res. Published online March 24, 2026. doi:10.1158/0008-5472.CAN-25-2487
2. New City of Hope and TGen study uncovers mechanism explaining how obesity increases cancer risk. News release. City of Hope. March 24, 2026. Accessed March 24, 2026. https://www.cityofhope.org/new-city-of-hope-and-tgen-study-uncovers-mechanism-explaining-how-obesity-increases-cancer-risk
3. Caffrey M. Can GLP-1 receptor agonists curb cancer? study links drugs to reduced risk in obesity-related cases. Am J Manag Care. 2025;31(spec 8):SP500-SP501.
4. Overweight and obesity: key facts. World Health Organization. December 8, 2025. Accessed April 13, 2026. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight