A Specific Link Is Found Between Red Meat Consumption and Colorectal Cancer

Scientists show that a form of DNA damage in cancer patients is associated with the consumption of red meat but not other foods or lifestyle factors. 

Scientists have discovered a molecular link between colorectal cancer and consumption of red meat, according to a study published in Cancer Discovery, a journal of the American Association for Cancer Research. 

While a link between colorectal cancer and red meat consumption has long been suggested, this is the first showing of a mechanistic link between the two.

The link is a mutational signature that indicates alkylation, a form of DNA damage. The alkylating signature was found in three large, long-term studies to be significantly associated with high pre-diagnosis consumption of red meat in patients with colorectal cancer. The signature was not, however, associated with pre-diagnosis intake of poultry or fish or with other lifestyle factors. Moreover, the signature was associated with cancer-causing mutations in the KRAS and PIK3CA genes commonly seen in colorectal cancers.

“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,” said Marios Giannakis, MD, PhD, an assistant professor of medicine at Harvard Medical School and a physician at Dana-Farber Cancer Institute. 

“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,” Giannakis said. “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.” 

To identify genetic changes associated with red meat intake, Giannakis and colleagues sequenced DNA from matched normal and colorectal tumor tissues from 900 patients with colorectal cancer who had participated in one of three nationwide prospective cohort studies, namely the Nurses’ Health Studies and the Health Professionals Follow-Up Study. All patients had previously provided information on their diets, lifestyles, and other factors over the course of several years prior to their colorectal cancer diagnoses. 

Analysis of DNA sequencing data revealed the presence of several mutational signatures in normal and cancerous colon tissue, including a signature indicative of alkylating DNA damage. The alkylating signature was significantly associated with pre-diagnosis intake of processed or unprocessed red meat, but not with pre-diagnosis intake of poultry or fish or with other lifestyle factors. 

The alkylating signature was also associated with patient survival: Patients whose tumors had the highest levels of alkylating damage had a 47 percent greater risk of colorectal cancer-specific death compared to patients with lower levels of damage, Giannakis said.

The researchers identified the KRAS and PIK3CA genes as potential targets of alkylation-induced mutation. Consistent with this prediction, they found that colorectal tumors harboring KRAS or PIK3CA mutations commonly observed in colorectal cancer had greater enrichment of the alkylating signature compared to tumors without these mutations. 

Giannakis explained that if physicians could identify individuals who are genetically predisposed to accumulating alkylating damage, these individuals could be counseled 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 greater risk of developing colorectal cancer or to detect cancer at an early stage. Because of 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.

This research was supported, in part, by the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant, which is co-administered by the AACR. Giannakis previously received a grant from the Colorectal Cancer Alliance, in partnership with the AACR, to support his research on biomarkers in colon cancer.