Gene-diet interactions may be responsible for colorectal cancer risk in red meat-eaters

A new study identifies two genetic variants that may determine one’s risk for the disease
Drs. Ulrike Peters and Li Hsu
Drs. Ulrike Peters and Li Hsu of the Public Health Sciences Division

The association of red and processed meat consumption with significant increased risk of colorectal cancer may be genetically based, according to research led by scientists Drs. Ulrike Peters and Li Hsu of the Public Health Sciences Division at Fred Hutchinson Cancer Research Center. The findings, presented today at the American Society of Human Genetics 2013 meeting in Boston, are based on the first study to identify gene-dietary interactions across a large population.

If the researchers’ findings are correct, it’s possible that eventually genetic screening could identify patients who are at higher risk for colorectal cancer so that diet modification and other prevention strategies could be adopted on an individual basis.

“However, although our findings are very interesting, it would be premature at this point to make this step. We are still at an early stage of this research investigating the interaction between genetic risk factors and lifestyle and environmental risk factors, such as diet, smoking or drug use,” Hsu said.

The researchers also found that genetic variants modified a lower colorectal cancer risk associated with a high intake of vegetables and low intake of processed meat. The study, which was conducted in coordination with researchers at the international National Institutes of Health-funded Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), involved more than 9,200 individuals with colorectal cancer and about 9,100 individuals without cancer who served as controls, all participants in 10 GECCO observational studies.

Researchers searched 2.7 million genetic variants to identify those associated with consumption of red meat and processed meat as well as fruits, vegetables and fiber. The participants’ medical history and diet were also correlated in the GECCO database.

They found a significant interaction between processed meat consumption and a genetic variant located on the same region of chromosome 10 that includes GATA3, a transcription factor previously linked to several forms of cancer that plays a role in the immune system. They also found a statistically significant diet-gene interaction in a variant on chromosome 8 that was associated with a reduced risk of colorectal cancer.

Researchers have not been able to establish how specific foods affect the activities of genes, but they speculate that digestion of processed meat may promote an immunological or inflammatory response that may trigger tumor development. The GATA3 transcription factor typically suppresses immunological or inflammatory response; however, the gene region that contains the genetic variant may encode a dysregulated transcription factor that impacts its ability to suppress the response.

According to Peters, the GECCO study may have important implications for understanding the underlying causes and biological pathways of cancer, including the possibility that genetic variants could help determine an individual’s risk for disease based on diet and other lifestyle and environmental risk factors. She said that while more investigation is required into how genes and diet interact, the findings represent an important new insight into the disease.

“These genetic loci have interesting biological significance given their location in the genome, and further functional analyses are required,” she said.

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