Know Your Biomarker: Tumor Sidedness - Why are they different?
Understanding the Roots of “Tumor Sidedness”
Most people think of colon cancer as a single disease. But today, doctors know that where a tumor starts in the colon can make a big difference in how it behaves, what symptoms it causes, and which treatments work best.
Tumor location, also called tumor sidedness, is a biomarker, meaning it provides important clues about the cancer’s biology and how to treat it. But that raises the question:
Why are right-sided and left-sided colon cancers so different in the first place?
Scientists have been studying this for years, and several key ideas help explain the origins (“etiology”) of these differences.
The Colon Begins as Two Different Parts in Early Life
One of the most surprising reasons right- and left-sided colon cancers differ is because the two sides of the colon come from different parts of the developing embryo.
- The right side (cecum, ascending colon, and first two-thirds of transverse colon) comes from an early structure called the midgut.
- The left side (last third of transverse colon, descending colon, and rectum) comes from something different—the hindgut.
This means that the cells on each side of the colon have different “starting instructions” built into them before a person is even born. A scientific study using hundreds of colon cancer samples found that the right and left sides have noticeable differences in how genes are turned on or off, and in the way cells process chemicals.
The Two Sides Are Exposed to Different Digestive Substances
As food is broken down and travels through the intestines, it changes form. On the right side, the contents are more liquid and contain more bile acids and nutrients. By the time they reach the left side, much of the water has been absorbed and the waste is more solid. The right and left sides are exposed to different chemicals from digestion. Over time, these differences may contribute to different types of cell damage and different paths to cancer.
The Microbiome (Your Gut Bacteria) Differs by Location
Your gut is home to trillions of bacteria that are part of your intestinal microbiome, the collective community of microbes in your colon. Many of them are helpful, some are potentially harmful. But these bacteria aren’t evenly spread throughout the colon.
The right and left sides of the colon have different microbiomes, that is, different populations of bacteria. The type of bacteria can vary, and the balance of one type of bacteria compared to another can vary. The bacteria at tumor sites can look different from the bacteria in healthy tissue.
Because bacteria can influence inflammation and cell growth, scientists believe that differences in microbiome communities may help explain why cancers behave differently depending on where they begin.
Tumor sidedness is a valuable biomarker, and the research supports it: embryonic origin, molecular pathways, and the microbiome all differ meaningfully between right and left CRC. These etiological factors don't just influence how the tumors form, but also how aggressive they are, what treatments they respond to, and ultimately, how likely a patient is to survive.
Understanding these roots helps clinicians, patients, and researchers appreciate why sidedness matters, and underscores the need for personalized approaches in colorectal cancer care.
For more information about tumor sidedness, please visit our Know Your Biomarker Tumor Sidedness page and check out the other blog posts in the series.