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Novel Gene-Diet Interaction May Explain Association Between Red and Processed Meat Consumption and Colorectal Cancer Risk

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Key Points

  • A significant interaction between processed meat consumption and the genetic variant rs4143094 was detected. The variant is located on the same chromosome 10 region that includes GATA3, a transcription factor gene previously linked to several forms of cancer.
  • On chromosome 8, a statistically significant diet-gene interaction was found in another variant, rs1269486, which was associated with reduced risk of colorectal cancer.
  • How specific foods affect the activities of genes has not been established, but the authors speculate that digestion of processed meat may promote an immunologic or inflammatory response that may trigger tumor development.

A newly discovered potential gene-diet interaction for colorectal cancer may shed light on the statistically significant increased risk of colorectal cancer that is associated with consumption of red and processed meat, according to a study reported yesterday at the American Society of Human Genetics 2013 meeting in Boston.

“If replicated, our findings have a relevant public health significance because diet is a modifiable risk factor for colorectal cancer,” said Jane Figueiredo, PhD, Assistant Professor of Preventive Medicine at the University of Southern California Keck School of Medicine, who presented the study at the ASHG meeting. The study is part of the ongoing NIH-funded Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO).

“It is conceivable that selected individuals at higher risk of colorectal cancer based on genomic profiling could be targeted for screening, diet modification, and other prevention strategies,” she added.

The scientists also determined that the lower colorectal cancer risk associated with vegetable, fruit, and fiber intake also was linked to genetic variants.

The possibility that genetic variants may modify an individual’s risk for disease based on diet has not been thoroughly investigated but represents an important new insight into disease development, said lead author Ulrike Peters, PhD, MPH, of the Public Health Sciences Division at Fred Hutchinson Cancer Research Center in Seattle.

According to the study’s lead biostatistician, Li Hsu, PhD, also of Fred Hutchinson, the study is the first colorectal cancer investigation with the statistical power to identify gene-dietary interactions across the genome of a large population of individuals.

Study Details

The study included a total of 9,287 patients with colorectal cancer and a control group of 9,117 individuals without cancer from 10 Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) observational studies.

Researchers systematically searched 2.7 million variants to identify those that were associated with the consumption of red meat and processed meat as well as fruits and vegetables.

A significant interaction between the genetic variant rs4143094 and processed meat consumption was detected; this variant is located on the same chromosome 10 region that includes GATA3, a transcription factor gene previously linked to several forms of cancer. The transcription factor encoded by this gene normally plays a role in the immune system.

On chromosome 8, a statistically significant diet-gene interaction was found in another variant, rs1269486, which was associated with reduced risk of colorectal cancer.

How specific foods affect the activities of genes has not been established. Drs. Peters and Figueiredo speculate that digestion of processed meat may promote an immunologic or inflammatory response that may trigger tumor development. The GATA3 transcription factor normally would help suppress the immunologic or inflammatory response. However, if the GATA3 gene region contains a mutation, it may encode a dysregulated transcription factor that impacts its ability to suppress the response.

Implications for Future Research

In addition to uncovering a novel gene-diet interaction for colorectal cancer, the GECCO study may have important implications for understanding the underlying causes and biologic pathways of cancer, said Dr. Peters.

“Our study highlights two genetic regions that are biologically interesting in cancer,” she said, referring to the variants located near GATA3 and at 8q23.3. “These genetic loci may have interesting biologic significance given their location in the genome, and further functional analyses are required.”

“GECCO aims to continue to discover additional colorectal cancer-related variants by investigating how genetic variants are modified by other environmental and lifestyle risk factors, including biomarkers as well as how they influence patient treatment response and survival,” Dr. Peters said.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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