This latest report also shows that people with a family history of colon cancer - who are therefore at higher risk for the disease - also benefit from the pain relievers.
"The [risk] reductions that we saw here are not inconsequential," said Dr. Elizabeth Ruder of the National Cancer Institute, the study's lead author.
"But we're not at the point that one could make a public health recommendation" based on the findings, she added.
Colon and rectal cancers are diagnosed in about 48 out of every 100,000 people in the US, according to the National Cancer Institute.
Together, these "colorectal" cancers are the third-leading cause of deaths from cancer.
Previous studies have found that aspirin is tied to a smaller risk of colon cancer.