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Mechanistic Link Between Eating Red Meat and Colon Cancer Revealed

NEW YORK (Reuters Health) – Red meat consumption has been consistently linked to an increased risk for colorectal cancer and a new study provides a mechanistic reason.

“Our study identified for the first time an alkylating mutational signature in colon cells and linked it to red meat consumption and cancer driver mutations,” Dr. Marios Giannakis with Dana-Farber Cancer Institute and Harvard Medical School in Boston said in a statement.

“These findings suggest that red meat consumption may cause alkylating damage that leads to cancer-causing mutations in KRAS and PIK3CA, thereby promoting colorectal cancer development. Our data further support red meat intake as a risk factor for colorectal cancer and also provide opportunities to prevent, detect, and treat this disease,” said Dr. Giannakis.

The study is published in Cancer Discovery, a journal of the American Association for Cancer Research.

The researchers analyzed DNA-sequencing data from matched normal and colorectal tumor tissues from 900 patients with colorectal cancer from the Nurses’ Health Studies and the Health Professionals Follow-Up Study. All patients had provided information on their diets, lifestyles and other factors over several years before being diagnosed with colorectal cancer.

They found a previously undescribed alkylating mutational signature, indicative of DNA damage, in normal and cancerous colon tissue.

This alkylating signature correlated significantly with a high intake of processed and unprocessed red meat prior to colorectal cancer diagnosis, but not with pre-diagnosis intake of poultry or fish or with other lifestyle factors.

Additionally, this mutational signature appeared to be driven by KRAS and PIK3CA genes.

Specifically, colorectal tumors harboring KRAS p.G12D, KRAS p.G13D, or PIK3CA p.E545K driver mutations, which are common in colorectal cancer, had greater enrichment of the alkylating signature relative to tumors without these cancer-driver mutations.

Patients whose tumors had the highest levels of alkylating damage had a 47% greater risk of dying of colorectal cancer than did patients with lower levels of damage.

“Although our study did not comprehensively examine for germline/inherited predisposing mutations to accumulation of the alkylating mutational signature in colon cells, future, larger studies with power to address this could (and should) be performed,” Dr. Giannakis told Reuters Health by email.

“One possible way to do this could be to have matched blood tests (for germline examination) with colon tissue (for mutational signature evaluation) from a larger number of individuals,” Dr. Giannakis said. “If such a germline mutation is identified, and after additional studies/data are obtained, it could be conceivable to suggest limiting/avoiding red meat intake as a precision prevention approach but we are not there yet/now.”

SOURCE: Cancer Discovery, online June 17, 2021.

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