For years, physicians have puzzled over why people with “clean” colonoscopies went on to develop colon cancer. With a new finding, OMRF’s Dr. David Jones may have solved this puzzle. The discovery could lead to a way to detect these cancers earlier and more effectively.
Trailing only lung cancer, colon cancer is the leading cause of cancer deaths for men and women, killing 65,000 Americans each year. Still, life expectancy improves considerably if the cancer is detected early: People whose colon cancer is discovered in the earliest stage have a 5-year survival rate of 90 percent, while those whose cancer is found in the latest stage have an 8 percent rate.
The most common method of screening is a colonoscopy, where doctors use a flexible scope to examine the colon. Yet physicians can miss certain cancer-causing polyps during these examinations.
“Some polyps are embedded in the surface of the colon, and they’re also flat and covered up,” says Jones, who holds the Jeannine Rainbolt Chair in Cancer Research at OMRF. “This makes them incredibly difficult for doctors to detect.”
For a long time, says Jones, it was thought colon cancers that developed in patients who had clean colonoscopies were coming about through some unknown mechanism that didn’t involve polyps. “Now it is clear these hidden polyps might be responsible for up to 30 to 40 percent of colon cancers that develop later,” he says.
Working with a team of researchers, Jones analyzed the genetic composition of the hidden polyps. “Most cancers—and most polyps—need more than one mutation to form. However, in these polyps, only one gene, called BRAF, was mutated,” he says.
Because of these telltale markers identifying the polyps, researchers could create a diagnostic test to analyze fecal samples to look for these changes prior to a colonoscopy. “If changes are present, it would be a way for the doctors to know to look for a hiding polyp,” says Jones.
Further analysis by the researchers also showed the mutation caused a wave of alterations in the DNA. “It’s probably the change in BRAF combined with these other changes that leads to polyps forming.”
The work was published in the scientific journal PLOS One. According to Jones, “It’s a huge step in the right direction that could have clinical relevance for patients in a meaningful way.” Next up, he says, are studies of how these genetic changes cause the cascade that ultimately leads to cancer.