Scientists at City of Hope and TGen, part of City of Hope, announced on Mar. 26 a major discovery explaining how excess weight increases the risk of cancer. Their findings, published in Cancer Research, reveal that as people gain weight, their organs grow larger by accumulating more cells. This increase in cell number may create more opportunities for DNA errors during cell division, which can lead to cancer.
The study is significant because it identifies a physical mechanism behind the well-known association between obesity and cancer. According to senior author Cristian Tomasetti, Ph.D., "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."
To investigate this connection, researchers examined CT scans from 747 adults across the full range of body mass index (BMI), measuring the size of each person's liver, kidneys and pancreas. They found that every five-point increase in BMI led to a 12% growth in liver size, a 9% increase in kidney size and a 7% rise in pancreas size. Further analysis showed over 60% of kidney growth was due to an increased number of cells—a process called hyperplasia—rather than just larger individual cells.
The research challenges earlier theories suggesting organ enlargement was mainly due to fatter cells rather than more numerous ones. Tomasetti said: "Think of playing the lottery: The more tickets you buy, the greater your chances of winning... 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 results indicate organ dimensions may be better predictors for certain cancers than BMI alone.
First author Sophie Pénisson, Ph.D., said: "When an organ doubles in size, it is expected to roughly double its risk of developing cancer... BMI is a poor proxy for telling us what the size of an organ is... Our work suggests that at least for some organs their dimensions may predict cancer risk better than BMI."
The researchers also stressed maintaining healthy weight from childhood onward since organs take time to grow and early-life obesity could give cells longer periods over which mutations might accumulate. Future studies will look into whether losing weight or using anti-obesity drugs such as GLP-1 medications could reduce both organ size and associated cancer risks.
Debbie C. Thurmond, Ph.D., director at City of Hope's Arthur Riggs Diabetes & Metabolism Research Institute said: "This exciting research deepens our understanding of how obesity may lead to cancer and highlights the role of organ growth in this process... It will be important to see if the new anti-obesity drugs can revert this process for cancer prevention."
