Colon cancer: first revealed how too much red meat modifies DNA, developing cancerous cells

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Elia Tabuenca García

For the first time, high consumption of processed and unprocessed red meat is associated with DNA damage in patients with colorectal cancer.

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For the first time, scientists associate high consumption of processed and unprocessed red meat with DNA damage in patients with colorectal cancer

How does the consumption of meat affect our health? Some scholars have linked a genetic mutation indicative of DNA damage to high red meat consumption and increased cancer-related mortality in colorectal cancer (CRC) patients. The findings, according to the scientists, could lead to the development of new diagnostic or CRC risk biomarkers and indicate therapeutic opportunities.

The study, published in Cancer Discovery, the scientific journal of the American Association for Cancer Research, and led by Marios Giannakis, professor of medicine at Harvard Medical School and oncologist at the Dana-Farber Cancer Institute, thus gives a more or less extensive than what has been argued for some time by many epidemiological studies.

These findings suggest that the consumption of red meat it can cause damage leading to cancerous mutations in KRAS and PIK3CA, thus promoting the development of colorectal cancer. Our data further support red meat intake as a risk factor for colorectal cancer and also offer opportunities to prevent, detect and treat this disease, says Giannakis.

We have known for some time that the consumption of processed meat and red meat is a risk factor for colorectal cancer, ”he explained. The International Agency for Research on Cancer said in 2015 that processed meat was carcinogenic and that red meat was likely carcinogenic to humans. Experiments in preclinical models have suggested that red meat consumption may promote the formation of carcinogenic compounds in the colon, but a direct molecular link with the development of colorectal cancer in patients has not been demonstrated. As Giannakis further stated, “What is missing is evidence that patients' colorectal cancers have a specific pattern of mutations that can be attributed to red meat. 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 new avenues for cancer prevention and treatment. '

A systematic review 

To identify genetic changes associated with red meat intake, the researchers performed whole exome sequencing on pairs of matched primary untreated tumor samples from 900 CRC patients who participated in three prospective studies (the Nurses' Health Studies I and II - NHS - and the Follow-up Study of Healthcare Professionals - HPFS). Each patient had previously provided information on their diet, lifestyle and other factors over the course of several years prior to the diagnosis of colorectal cancer, and to check whether dietary components contributed to the alkylating signature in the CRC, they exploited repeated measurements collected. prospectively of meat, poultry and fish consumption in grams per day in the NHS and HPFS cohorts.

The team's 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 prediagnostic intake of processed or unprocessed red meat, but not with prediagnostic intake of poultry or fish, or other lifestyle factors. 

And in contrast to the results for red meat consumption, other dietary variables (fish and chicken intake) and lifestyle factors, including body mass index, alcohol consumption, smoking, and physical activity, did not show any significant association with the alkylating signature.

Using a predictive model, the researchers identified the KRAS and PIK3CA genes as potential targets for the alkylation-induced mutation. Consistent with this prediction, they found that colorectal cancers that harbored KRAS G12D, KRAS G13D, or PIK3CA E545K driver mutations, which are commonly observed in colorectal cancer, had greater enrichment of the alkylating signature than tumors without these. mutations.

The analysis shows that DNA damage can affect the KRAS gene, in particular for two mutations (G12D and G13D) and the PIK3CA gene, both of which are already associated with colorectal cancer. But according to Giannakis, the concatenation of possible causal events is still long:

We have formally observed the association between red meat and alkylation mutations. Then we know that these mutations impact the KRAS gene and that the KRAS mutation can cause cancer.

Which means that additional genetic factors could be found that could lead to an increase or a reduction in the amount of damage that different individuals accumulate for the same amount of red meat consumed. This will require more research to understand the biology behind the development of tumors. But one fact seems to be constant: red meat remains a risk factor for colorectal cancer and other types of cancer.

Fonte: Cancer Discovery

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