Research Identifies Potential Cause for Red Meat-Colorectal Cancer Link

A study in PLOS One suggests that interactions between N-acetyltransferase 2 (NAT2) and consumption of red meat may result in increased risk of colorectal cancer (CRC). The finding comes on the heels of several well-publicized studies earlier this year linking CRC to cooked red meats.

Sedentary lifestyles and obesity are contributing to increases in the prevalence of CRC worldwide. Red meat and processed meat consumption are at this point established risk factors for the development of CRC, but exactly how and why red meats increase the risk is not yet well understood.

Earlier research has suggested that exposure to heterocyclic aromatic amines (HAAs), which are formed when meat is cooked at high temperature for a long duration, may be partly to blame. NAT2 has been shown to play a critical role in the bioactivation of HAAs.

Ethnic make-up has an impact on variations in NAT2 phenotypes. Japanese and African Americans have high rates of CRC and a frequency of rapid acetylator phenotype, which is 10- and 2-fold greater than in whites, respectively.

“It is notable that populations with the highest frequencies for the rapid acetylation phenotype also have the highest CRC incidence rates in the world (Native Alaskans and Japanese Americans), and those with the lowest rapid acetylation phenotype frequencies have very low CRC rates (e.g., in North Africa),” the researchers observed. “Moreover, the raising trends in colon cancer incidence and mortality in Japan have closely paralleled the increase in red meat intake with a 20 year lag.”

The current meta-analysis looked at 4 studies of Japanese (2,217 CRC cases and 3,788 controls) and 3 studies of African Americans (527 CRC cases and 4,527 controls). NAT2 phenotype was inferred from an optimized seven—SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P’s ≤ 0.002). The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype.

“The interactions for processed meat and total red meat appeared to be dose-dependent since their associations with CRC were strongest among individuals with the rapid NAT2 phenotype, intermediate among individuals with the intermediate NAT2 phenotype, and non-significant among those with the slow NAT2 phenotype,” the study authors noted.

Still, despite the statistically significant finding, much additional research will be needed to confirm the finding and consider other confounding factors, such as the cooked temperature of the meat consumed, and other factors that contribute to high NAT2 activation, among many other variables.

“This large study provides substantial support for a role of NAT2 in modifying the association between intake of red meat and, particularly, processed meat and colorectal cancer risk in Japanese and African Americans, two populations at high risk for this disease,” the researchers concluded. “Lowering consumption of red meat, especially processed meat, may be an effective approach for CRC prevention in these and other populations with a high frequency of the rapid NAT2 phenotype.”