LOS ANGELES– Researchers from City of Hope and TGen have identified a key biological mechanism explaining how obesity increases the risk of cancer, finding that excess body weight leads to larger organs with more cells, raising the likelihood of cancer-causing mutations.
The study, published in the journal Cancer Research, shows that as individuals gain weight, their organs expand by accumulating more cells to meet increased energy demands. This growth increases the number of cell divisions, raising the chances of DNA errors that can lead to cancer.
“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 Cristian Tomasetti, Ph.D., senior author of the study and director of City of Hope’s Center for Cancer Prevention, Early Detection and Monitoring.
To investigate the link, researchers analyzed 747 adults across the full spectrum of body mass index (BMI), using CT scans to measure the size of the liver, kidneys, and pancreas. The study found that organ size increased consistently with body weight. For every five-point rise in BMI, the liver grew by 12 percent, kidneys by 9 percent, and the pancreas by 7 percent.
The team also examined kidney tissue samples and biopsy data, finding that more than 60 percent of organ growth was due to an increase in the number of cells, a process known as hyperplasia, rather than just enlargement of existing cells.
This finding challenges earlier assumptions that larger organs in obese individuals were primarily due to fat accumulation. Instead, the increase in cell number raises the probability of mutations and uncontrolled growth.
“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.”
The study demonstrated a strong correlation between organ enlargement and cancer risk, supporting the idea that increased cell counts are a major driver of tumor development in obesity, alongside other known factors such as inflammation and hormonal changes.
Researchers also suggested that organ size may be a more accurate predictor of cancer risk than BMI alone, which does not distinguish between fat and lean tissue.
“When an organ doubles in size, it is expected to roughly double its risk of developing cancer,” said Sophie Pénisson, Ph.D., first author of the study and associate professor at TGen.
The findings highlight the importance of maintaining a healthy weight early in life, as long-term exposure to increased cell division may raise cancer risk over decades.
“Organs take time to grow, and it can take decades for cells to turn malignant,” Tomasetti said. “Childhood obesity gives organ cells a longer runway to accumulate mutations and evolve into something worse.”
Future research will explore whether weight loss can reverse organ growth and reduce cancer risk, as well as the potential impact of new anti-obesity medications.
“This exciting research deepens our understanding of how obesity may lead to cancer and highlights the role of organ growth in this process,” said Debbie C. Thurmond, Ph.D., director of the Arthur Riggs Diabetes & Metabolism Research Institute at City of Hope.
