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He and his team analyzed blood and tissue samples from the tumors of nearly 1,000 colorectal cancer patients across 11 countries, including Canada, Japan, Thailand, and Colombia. They used DNA sequencing technology to identify cellular mutations, or genetic changes that can help cancer form, grow, and spread.
“Different carcinogens leave this characteristic pattern of mutations, which we call mutational signatures,” Alexandrov explains. “The simplest example is if you smoke cigarettes, you get a specific pattern of mutations across your lung cells.”
Alexandrov and his team found that people diagnosed with colorectal cancer under the age of 50 had a “striking enrichment” of mutations associated with colibactin. The younger the person was, on average, the higher the prevalence of these signatures. Those diagnosed with colorectal cancer under age 40 were about three times more likely to have colibactin-driven mutations than those diagnosed after age 70.
“When we sequence cancers, we see this archeological record of everything that happened in that person’s lifetime,” Alexandrov says. Meaning, scientists can figure out the approximate timing of when specific mutations took hold in the gut.
The study’s results suggest that the participants’ colibactin exposure happened before they turned 10. This early “hit” to the gut microbiome seemed to put people 20 to 30 years ahead of schedule for developing colorectal cancer, Alexandrov says. Rather than being diagnosed in their 60s or 70s, they faced the disease in their 30s or 40s.
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