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Bladder Cancer Risk Increased With 2 Components Of Red Meat Combined With Alteration In DNA Repair

October 18, 2012

Two components of red meat – dietary protein and dietary iron – may combine to form powerful carcinogens, N-nitroso compounds, which increase risk for bladder cancer. Moreover, individuals with reduced ability to reverse the effects of N-nitroso compounds because of a genetic variation in their RAD52 gene could be at particularly high risk.

Chelsea Catsburg, a doctoral student at the Keck School of Medicine of the University of Southern California, Los Angeles, presented these data at the 11th Annual AACR International Conference on Frontiers in Cancer Prevention Research, held here Oct. 16-19, 2012.

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, 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.”

Catsburg 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, they examined whether genetic variation in DNA repair enzymes, available to correct the damage caused by these endogenously formed carcinogens, modified these associations.

The researchers tested 627 single-nucleotide polymorphisms in 27 genes involved in N-nitroso compound metabolism or DNA repair. They collected data from 355 bladder cancer cases and 409 controls in the Los Angeles Bladder Cancer Study.

“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.

“This study suggests that these exposures may also affect secondary organs such as the bladder,” Catsburg said. “Individuals at risk for bladder cancer may wish to avoid intake of red and processed meats, especially if they have genetic polymorphisms that reduce DNA repair activity and make them more vulnerable to the effects of carcinogens.”

Further replication of this study to support an association between heme and meat intake and the risk for bladder cancer is necessary, she added.

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