Red meat consumption may promote DNA damage-associated mutations in patients with colorectal cancer
While many different risk factors for colorectal cancer (CRC) have been established, the underlying mechanisms are not well known. A recent study published in Cancer Discovery (journal for American Association for Cancer Research) found that high red meat consumption was linked to higher levels of DNA damage in colon cells, driving CRC-specific mutations and greater cancer-related mortality in patients with CRC.
In 2015, the International Agency for Research on Cancer declared that processed meat was carcinogenic, and that red meat was probably carcinogenic to humans[1]. Preclinical studies have suggested that red meat consumption may promote the development of cancer-causing compounds in the colon, though a direct link to CRC development through specific mutations has not been shown.
The Study
The investigators sequenced DNA from normal and CRC tissues from 900 patients with CRC from large, prospective studies: the Nurses’ Health Studies and the Health Professionals Follow-up Study. Information on patients’ diet, lifestyle, and other factors were collected over the course of several years before their CRC diagnoses. Through DNA sequencing analysis, several mutational signatures or patterns were identified.
A strong association was found between levels of DNA alkylation and pre-CRC diagnosis intake of processed or unprocessed red meat. The study investigators also found that higher incidence of alkylating damage was found in the distal colon (descending and sigmoid colon) compared to the proximal colon (cecum, ascending and transverse colon).
The researchers used predictive models to identify which CRC-related genes were potential targets of mutation by alkylation. Both KRAS and PIK3CA, two mutations commonly mutated in CRC, were more likely to show evidence of alkylation compared to tumours without these mutations. Furthermore, the presence of higher levels of alkylating damage was linked to greater risk of CRC-specific death (47% increase) compared to patients with lower levels of alkylating damage.
Conclusions & Future Directions
The study is the first to show how a specific mutational pattern (alkylation) in the DNA of colon cells is linked to red meat consumption and the mutations that drive CRC. The findings suggest that red meat consumption may cause alkylating damage, resulting in cancer-causing mutations in KRAS and PIK3CA, therefore promoting CRC development.
The study investigators note that the alkylating mutational signature could potentially be used as a biomarker in the future to better identify patients who are at greater risk of developing CRC or to help detect the presence of CRC at an earlier age. Since the alkylating signature is also linked to patient survival, it may also have potential as prognostic biomarker.
Take away message:
Study findings show that high red meat consumption was linked to higher levels of DNA damage in colon cells, driving mutations that are specific to the development of colorectal cancer. High red meat consumption was also linked to greater mortality among patients with CRC. Levels of DNA damage increased with increased consumption of red and processed meat.
[1] IARC Monographs evaluate consumption of red meat and processed meat
https://www.iarc.who.int/wp-content/uploads/2018/07/pr240_E.pdf
