Rx Nutrition Resource Center

Rx Nutrition Resource Center

Disclosures: The NIH, Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant, Project P Fund, Cancer Research UK Grand Challenge Award, Nodal Award from Dana-Farber Harvard Cancer Center, Friends of the Dana-Farber Cancer Institute, Bennett Family Fund and Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance and Stand Up to Cancer supported this study. Giannakis reports research funding from Bristol Myers Squibb, Merck, Servier and Janssen, unrelated to this study.
June 28, 2021
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’Mounting’ data link red meat consumption to colorectal cancer risk, mortality

Disclosures: The NIH, Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant, Project P Fund, Cancer Research UK Grand Challenge Award, Nodal Award from Dana-Farber Harvard Cancer Center, Friends of the Dana-Farber Cancer Institute, Bennett Family Fund and Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance and Stand Up to Cancer supported this study. Giannakis reports research funding from Bristol Myers Squibb, Merck, Servier and Janssen, unrelated to this study.
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Researchers have identified a possible molecular link between high consumption of both processed and unprocessed red meat and increased colorectal cancer risk and mortality.

“We have known for quite a while now that environmental factors, including diet, can impact colorectal cancer incidence. What was missing were data demonstrating whether we could see an impact of these environmental carcinogens in cancer specimens of patients,” Marios Giannakis, MD, PhD, oncologist at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School, said during an interview with Healio. “This research adds to lines of evidence connecting high consumption of red meat to colorectal cancer risk. The ponderous evidence is mounting.”

Marios Giannakis, MD, PhD, oncologist at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School

Giannakis and colleagues sought to identify genetic alterations associated with red meat consumption by sequencing DNA from matched normal and colorectal cancer tissue of 900 participants in the Nurses’ Health Studies and the Health Professionals Follow-up Study.

According to study results, published in Cancer Discovery, an alkylating mutational signature in colon cells appeared associated with consumption of red meat and certain cancer driver mutations.

Healio spoke with Giannakis about the study, what he and colleagues found, what surprised him most about the findings and next steps for research.

Healio: What prompted this research?

Giannakis: We wanted to determine whether we could establish a closer link between environmental risk factors for colorectal cancer and the mutations that we find in colorectal cancer.

Healio: What new information does this study provide?

Giannakis: By examining sequencing data of 900 patients with colorectal cancer, we identified a previously undescribed pattern of mutations — a “mutational signature” — that exists in colorectal cancer. We attributed this signature to alkylating damage and next investigated for possible culprits.

One of the known risk factors for colorectal cancer is red meat, and it is known to contain chemicals that potentially can cause alkylation. We essentially found that patients who were consuming the most red meat overall, including both processed and unprocessed red meat, had cancers with increased alkylating damage.

What may be harder to learn is exactly how much is too much red meat consumption. There may be some patients who eat a lot of red meat and are never diagnosed with colorectal cancer, just as there are long-term smokers who will not be diagnosed with lung cancer. Conversely, even a vegan may be diagnosed with colorectal cancer and a nonsmoker may be diagnosed with lung cancer — red meat consumption is not the only risk factor that leads to colorectal cancer.

We also know that certain KRAS mutations are critical in the development of colorectal cancer, and it appears in our study that these mutations can be attributed to alkylating damage in most cases.

Healio: Did any of your findings surprise you?

Giannakis: We were a little surprised to learn that not only processed but also unprocessed red meat was associated with this pattern of mutations. Processed meat is a class 1 carcinogen, according to International Agency for Research on Cancer, but unprocessed red meat, which is currently labeled as probably carcinogenic, was also associated with alkylating damage.

Of note, in our study an individual had to be an extreme consumer of red meat prior to diagnosis. It was the patients in the top 10% of red meat consumption (median amount, > 150 g per day) who had enrichment of these mutations in their tumors. This was not the case with chicken or fish. So, there does appear to be a specific association between red meat and alkylating damage.

Healio: What should oncologists do with this information?

Giannakis: We must be careful in the way that we interpret these results because we do not want to scare people, but we also cannot sit back and ignore them. The accumulation of evidence is mounting. Individuals should consume a balanced diet, rich in fruits and vegetables, and avoid high intake of red meat.

Healio: Are there plans for additional research?

Giannakis: One of the next steps is to further investigate the mechanism by which increased red meat consumption can cause these mutations and explore what other factors modify this risk.

For more information:

Marios Giannakis, MD, PhD, can be reached at Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215; email: marios_giannakis@dfci.harvard.edu.