Eating red meat may promote mutations associated with DNA damage in patients with colorectal cancer


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Genetic mutations indicative of DNA damage were associated with high red meat consumption and increased cancer mortality in colorectal cancer patients, according to a study published in Discovery of cancer.

“We have known for a long time that the consumption of processed meat and is a risk factor for colorectal said Marios Giannakis, MD, Ph.D., assistant professor of medicine at Harvard Medical School and physician at the Dana-Farber Cancer Institute. The International Agency for Research on Cancer stated that processed meat was carcinogenic. and that red meat was likely carcinogenic to humans in 2015.

Experiments in preclinical models have suggested that consumption of red meat may favor the formation of carcinogenic compounds in the colon, but no direct molecular link has been shown with the development of colorectal cancer in patients, Giannakis explained. “What is missing is a demonstration that “Patients have a specific pattern of mutations that can be attributed to red meat,” he said. “Identifying these molecular changes in colon cells that can cause cancer would not only support the role of red meat in the development of colorectal cancer, but would also provide a pathway for cancer prevention and treatment.”

To identify the genetic changes associated with red meat intake, Giannakis and colleagues sequenced the DNA of normal and colorectal tumor tissue from 900 colorectal cancer patients who had participated in one of three prospective cohort-level studies. namely health studies of nurses and health professionals. Follow-up study. All patients had previously provided information about their diets, lifestyles, and other factors for several years prior to colorectal cancer diagnoses.

Analysis of the DNA sequencing data revealed the presence of several mutational signatures in normal and cancerous colon tissue, including a signature indicative of alkylation, a form of DNA damage. The alkylating signature was significantly associated with pre-diagnosis intake of processed or unprocessed red meat, but not with pre-diagnosis of poultry or fish diagnosis or other lifestyle factors. Red meat consumption was not associated with any of the other mutational signatures identified in this study. In line with previous studies linking red meat consumption to the incidence of distal colon cancer, Giannakis and colleagues found that normal, cancerous tissue in the distal colon had significantly higher alkylating damage than distal colon cancer. proximal colon.

Using a predictive model, the researchers identified the KRAS and PIK3CA genes as potential targets of the alkylation-induced mutation. Consistent with this prediction, they found that colorectal tumors containing mutations in the KRAS G12D, KRAS G13D, or PIK3CA E545K controller, commonly seen in colorectal cancer, showed greater enrichment of the alkylating signature compared to tumors without colorectal cancer. these mutations. Alkylating signature was also associated with patient survival: patients whose tumors had the highest levels of alkylating damage had a 47 percent higher risk of death from colorectal cancer than patients with lower levels of colorectal cancer. damage.

“Our study first identified an alkylating mutational signature in colon cells and related it to red meat consumption and cancer-causing mutations,” Giannakis said. “These findings suggest that red meat consumption may cause alkylating damage leading to cancer-causing mutations in KRAS and PIK3CA, thus promoting the development of colorectal cancer. Our data support red meat intake as a cancer risk factor.” colorectal and also offer opportunities to prevent, detect and treat this disease. “

Giannakis explained that if doctors could identify individuals who are genetically predisposed to accumulating alkylating damage, these individuals could be advised to limit red meat intake as a form of precision prevention. In addition, the alkylating mutational signature could be used as a biomarker to identify patients at increased risk of developing colorectal cancer or to detect cancer in an early stage. Due to its association with patient survival, the alkylating signature may also have potential as a prognostic biomarker. However, future studies are needed to explore these possibilities, Giannakis noted.

One limitation of the study is the potential selection bias of study participants, as tissue samples from all cases of colorectal cancer incident in cohort studies could not be recovered. Current studies by Giannakis and colleagues are exploring the potential role of red ingestion and alkylating damage in various patient groups.

Red meat consumption, bad manners related to colorectal cancer

More information:
Discovery of cancer (2021). DOI: 10.1158 / 2159-8290.CD-20-1656

Citation: Red meat consumption may favor mutations associated with DNA damage in patients with colorectal cancer (2021, June 17) recovered on June 17, 2021 at red-meat-consumption-dna-damage -assoc.html

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