New research from the Keck School of Medicine of USC suggests that two components of red meat — dietary protein and dietary iron — may combine to form powerful carcinogens that increase risk for bladder cancer.
According to the researchers, individuals with reduced ability to reverse the effects of these so-called N-nitroso compounds because of a genetic variation in their RAD52 gene could be at particularly high risk.
Chelsea Catsburg, a molecular epidemiology doctoral student at the Keck School and first author of the study, presented these findings at the 11th annual AACR International Conference on Frontiers in Cancer Prevention Research, held this week in Anaheim, Calif.
Dietary protein is made up of amino acids, which can be naturally metabolized into biogenic amines, according to Catsburg.
Research has shown that the processing and storage of meat increases amine concentrations. When these amines are in the presence of nitrites, they generate nitrosamines, which have carcinogenic properties. In addition, heme iron, which is found in red meat, has been shown to increase the formation of nitrosamines from amines.
“Nitrosamine formation occurs predominantly in the stomach and intestines, so these exposures have been studied extensively in relation to gastric cancer and somewhat in relation to colorectal cancer,” Catsburg said. “However, there is evidence that these reactions also take place in the bladder, particularly in the presence of infection.”
Mariana Stern, associate professor of preventive medicine at USC who directed this study, and colleagues had previously found that meat groups with high heme and high amine concentrations, such as salami and liver, increased risk for bladder cancer.
In this study, Catsburg examined whether genetic variation in DNA repair enzymes, which typically correct the damage caused by these endogenously formed carcinogens, modified these associations.
The researchers, who collected data from 355 bladder cancer cases and 409 controls in the Los Angeles Bladder Cancer Study, tested 627 single-nucleotide polymorphisms in 27 genes involved in DNA repair.
“We found that a polymorphism in the RAD52 gene modified the effect of these exposures,” Catsburg said. “This polymorphism is suspected to reduce the DNA repair activity of the RAD52 protein, and the association of these meat groups and bladder cancer risk was significantly higher in individuals with one or more copies of this polymorphism.”
These results further support recommendations by the World Cancer Research Fund to limit red meat intake and to avoid processed meats to reduce risk for stomach and bowel cancer, according to the researchers.
“Our previous research has shown that red meat may increase risk of other cancers,” Stern said. “This study suggests that the bladder may also be affected. While we cannot make any health recommendations based on this study alone, those who are at risk for bladder cancer may want to limit their intake of red and processed meats.”
Co-authors of the study included Roman Corral, Juan Pablo Lewinger, Amit Joshi, Manuela Gago-Dominguez, Esteban Castelao, David Vandenberg, Jian-Min Yuan, Victoria Cortessis and Malcolm Pike.
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