For many years, doctors have noticed something unusual.
People who develop dementia often seem less likely to develop cancer, while people who have had cancer appear to have a lower chance of developing dementia later in life.
Scientists have repeatedly observed this pattern, but no one has fully understood why it happens.
Now, researchers at the University of Kentucky Sanders-Brown Center on Aging believe they may have found an important clue.
Their new study suggests that one small change in a gene called GRN may influence the risk of both diseases—but in completely opposite ways. The research was published in the Journal of Neuropathology & Experimental Neurology.
Genes are small pieces of DNA that contain instructions for how our bodies grow and function. The GRN gene produces a protein called progranulin.
This protein helps cells grow, repair damage, control inflammation, and communicate with each other. Because progranulin is active in many parts of the body, changes in the GRN gene may affect several diseases at once.
The research team focused on a common genetic variant called rs5848. A genetic variant is simply a small difference in DNA that naturally exists among people.
The scientists found that people carrying one version of this variant had a higher risk of developing LATE, a common type of dementia that mainly affects adults over the age of 85. Surprisingly, the same genetic variant was linked with a lower risk of developing cancer.
LATE, which stands for limbic-predominant age-related TDP-43 encephalopathy, is less well known than Alzheimer’s disease but is actually very common in older adults. Its symptoms are very similar to Alzheimer’s, including memory loss and problems with thinking, making it difficult for doctors to tell the two conditions apart while a person is alive.
Previous studies by the same research group had already found that people with a history of cancer often had fewer Alzheimer’s-related brain changes after death. The new findings provide a possible biological explanation for this long-standing mystery.
The researchers believe progranulin may play opposite roles in different diseases. Higher levels of the protein appear to help cancer cells survive and grow. Lower levels may allow harmful proteins to build up inside the brain, increasing the risk of LATE dementia. This means that changing progranulin levels could help one disease while making another disease worse.
The study also found important differences among ancestry groups. The dementia-linked version of the GRN variant was more common among Black Americans, while the version linked with lower cancer risk was more common among white Americans. The researchers say this highlights why it is important to include people from many different backgrounds in medical research.
These discoveries may also influence future treatments. Several experimental medicines are being developed to increase progranulin levels to protect the brain. However, if higher progranulin also encourages cancer growth, doctors will need to carefully balance the possible benefits and risks before using these treatments widely.
Although the findings are exciting, the study does not mean that one gene alone determines whether someone will develop dementia or cancer. Many other genes, lifestyle habits, age, and environmental factors also influence disease risk.
The research was published in the Journal of Neuropathology & Experimental Neurology.
This study is important because it moves beyond simply observing that dementia and cancer rarely occur together and offers a possible biological explanation. However, the research identifies an association rather than proving direct cause and effect.
Future laboratory studies and clinical research will be needed before these findings can lead to new treatments. Even so, the discovery provides valuable insight into how one genetic pathway may affect two major diseases in opposite directions.
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