The study discovered a unique mutational signature—a pattern that had never been seen previously but was indicative of a form of DNA damage known as “alkylation.”
Although it is common medical advice to consume less red meat to avoid colorectal cancer, the mechanism by which it causes cells to change has remained a mystery, and not all scientists felt convinced there was a significant relationship.
A recent study published in the journal Cancer Discovery has revealed particular patterns of DNA damage induced by red meat-rich diets, further exposing the food as a carcinogen and opening the door to early detection and therapy design.
Prior studies that established the link were mostly epidemiologic, meaning that people who had the disease were polled about their eating habits, and researchers discovered links to colorectal cancer incidence.
The evidence wasn’t a slam dunk, however, due to a lack of clarity in the biology, and in 2019, one group of researchers made headlines when they stated they only had a “low” degree of assurance that lowering intake would reduce cancer deaths.
“When we say red meat is carcinogenic, and that it impacts incidence of cancer, there has to be some plausible way by which it does it,” Dana-Farber Cancer Institute oncologist Marios Giannakis, who led the new study, told AFP.
To fill the information deficit, Giannakis and his colleagues analyzed DNA data from 900 colorectal cancer patients who were selected from a wider sample of 280,000 health professionals who took part in a year-long study that included lifestyle surveys.
Rather than asking people to recall their eating habits after they were ill, this technique had the advantage that the people documenting their diet had no way of knowing about their potential cancer diagnosis. The study discovered a unique mutational signature—a pattern that had never been seen previously but was indicative of a form of DNA damage known as “alkylation.”
These alterations aren’t seen in all malignant cells, and the signature was found in some healthy colon samples as well. Prior to the patient’s cancer diagnosis, the mutation profile was strongly linked to red meat consumption, both processed and unprocessed, but not to poultry, fish, or any of the other lifestyle variables studied.
“With red meat, there are chemicals that can cause alkylation,” explained Giannakis.
The chemicals at question include nitroso compounds, which may be formed from heme, which is abundant in red meat, and nitrates, which are commonly present in processed meat. The mutation patterns were significantly connected to the distal colon, which is the bottom section of the intestines that leads to the anal canal, and where previous studies showed colon cancer linked to red meat occurred most frequently.
Furthermore, the genes most impacted by the alkylation patterns were those that have previously been found to be among the most common drivers of colorectal cancer when they change, according to prior studies. The many lines of evidence, when taken together, provide a convincing case, according to Giannakis, who compares the research to meticulous detective work.
The worrisome mutation profile had a lot to answer for in this case: individuals with the greatest levels of alkylation damage in their tumors had a 47 percent higher chance of colorectal cancer-specific mortality than patients with lower levels of damage. However, Giannakis, who is also a practicing doctor, believes it is critical to concentrate on how the study may benefit people.
Future research might help doctors determine whether individuals are genetically prone to alkylation damage and advise them to restrict their red meat consumption. Identifying individuals who have already begun to accumulate the mutational signature might aid in determining who is more likely to acquire cancer or catching the disease at an earlier stage.
Furthermore, because alkylation damage appears to be a biomarker of patient survival, it might be utilized to inform patients about their prognosis. Finally, knowing the biochemical route through which colorectal cancer develops allows for the development of drugs that halt or reverse the process, therefore preventing the illness.
The major message, according to Giannakis, is not that people should completely avoid red meat: “My recommendation would be that moderation and a balanced diet is key.” Only patients who consumed more than 150 grams (five ounces) of food per day, about two or more meals, had high levels of tumor alkylation damage.