Not all colon cancers are the same

The human colon is a five-foot-long pipe, and colon cancer can develop anywhere along it. What you may not know is that where colon cancer develops can make a difference in treatment and survival odds.

Right-sided colon cancer has been increasing in prevalence, and it can be more aggressive and harder to treat than left-sided colon cancer, according to surgeon Ryan Carlson, MD, who specializes in colorectal surgery and practices at Cape Cod Healthcare General and Specialty Surgery and Cape Cod Hospital.

There are a few reasons why right-sided colon cancers occur, he said. First of all, the right side of the colon is exposed to different bacteria and chemicals than the left side. As the food moves through the digestive system it goes from the stomach to about 10 to 12 feet of small intestine before entering the right colon, the transverse colon, left colon and out the rectum.

“On the right side, that’s where most of the bile acids are exposed and, as the stool goes through, those bile acids get conjugated to other materials and they get absorbed passively in the colon wall,” he said. “When they do that, we think they can damage the DNA sometimes and that can lead to cellular damage and lead to cancer.”

Sixty percent of Americans and 70 percent of Massachusetts residents get colon cancer screening with either a colonoscopy or a DNA test. That leaves 30 to 40 percent of people who do not get screened. For those folks, the only way to detect colon cancer is through symptoms. The two main symptoms are bleeding and pain from obstruction.

“It’s harder to detect blood from the right side, because as blood goes through the colon it doesn’t become red anymore,” Dr. Carlson said. “It becomes dark brown or even black, so it’s tougher to pick up bleeding on the right side. Bleeding in this case is kind of good because it’s like a warning sign that something is wrong.”

The other problem is the stool is a watery consistency in the right side of the colon. That means if there is a mass, the stool isn’t rubbing against it causing it to bleed. The right side of the colon is also wider than the left side. Since the stool is so watery, even if there is a blockage of 90 percent, the stool could still pass through and the patient wouldn’t get the crampy pain that can accompany colon cancer on the left, he said.

Three Pathways

There are three pathways to colon cancer: chromosomal instability, microsatellite instability and serrated polyps. Chromosomal instability is mostly a characteristic of left-sided colon cancer, while microsatellite instability is mostly right-sided. Tumors with microsatellite instability do not properly detect and repair mismatched DNA, so they replicate mutations.

“Traditionally right-sided ones have done worse because that microsatellite leads to mutations in the BRAF gene and the KRAF gene. Because those genes were mutated, some of the chemotherapy didn’t work for those cancers because it was targeted to a receptor that downstream went to those genes.” Dr. Carlson said.

But sometimes, the right-sided microsatellite instability can be easier to treat because their instability causes them to produce a lot more antigens that the immune system can see and target and destroy the cancer. Plus, these days, there are better treatments like immunotherapy or check-point inhibitors. They activate the immune system and the T cells which can destroy the cancer, he said.

When Dr. Carlson was doing his residency, it wasn’t unusual for a surgeon to look at a CT scan and tell someone with stage 4 cancer that they had about six months to live. But if they have microsatellite instability stage 4 cancer, now they can be treated with the drug pembrolizumab and live for years, he said.

Things You Can Do

Colon cancer is on the rise in the United States, and more people are getting it at younger ages. Doctors don’t know why this is true, but Dr. Carlson said the likeliest reason is something environmental like our predilection for processed foods or our exposure to “forever” chemicals.

Modifiable risk factors to avoid colon cancer include:

• Avoid eating red meat
• Avoid eating processed meats that contain nitrates
• Limit or eliminate alcohol
• Exercise regularly
• Eat more fruits and vegetables

“I tend to think if something is good, then a whole lot more of it is really, really good, but it doesn’t seem that is necessary for colon cancer,” Dr. Carlson said. “As long as you get four to six servings of vegetables a day and eat whole grains, that seems to be enough protection.”

But he cautions that while those modifiable risk factors are helpful, they max out their effectiveness at around 20 to 30 percent.

“It all adds up for sure, but I always tell my patients in clinic that the biggest modifiable risk is the colonoscopy,” he said. “That’s been shown again and again to decrease the risk of dying from colon cancer by 80 percent and some studies say 88 percent. If you could choose to do one thing, whether it’s exercise more, eat a better diet or stopping drinking, choose a colonoscopy.”