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How high-fat diet causes colorectal cancer, by researchers

By Chukwuma Muanya, Assistant Editor   |   11 July 2017   |   3:52 am  

Researchers from the Cleveland Clinic in Ohio, United States (U.S.), have identified a cellular signaling pathway, called JAK2-STAT3, that drives the growth of cancer stem cells in the colon in response to a high-fat diet. PHOTO CREDIT: google.com/search

*Increased fish, fruit consumption with low intake of soft drinks reduces risk

A new study suggests a molecular explanation for the link between a high-fat diet and colorectal cancer. While the evidence of a link between an unhealthful diet and colorectal cancer is robust, the underlying mechanisms for this association have been unclear. A new study, however, may have uncovered an explanation.

Researchers from the Cleveland Clinic in Ohio, United States (U.S.), have identified a cellular signaling pathway, called JAK2-STAT3, that drives the growth of cancer stem cells in the colon in response to a high-fat diet.

What is more, the researchers found that blocking the JAK2-STAT3 pathway in mice fed a high-fat diet halted the growth of these stem cells, a finding that might fuel the development of new drugs to treat colorectal cancer.


Study co-author Dr. Matthew Kalady, co-director of the Comprehensive Colorectal Cancer Program at the Cleveland Clinic, and colleagues recently reported their findings in the journal Stem Cell Reports.

In recent years, a wealth of studies have suggested that a high-fat diet is a risk factor for colorectal cancer. However, the precise mechanisms behind this association have been ambiguous.

With the hope of shedding light on such mechanisms, Dr. Kalady and colleagues investigated how a high-fat diet influences JAK2-STAT3, a cellular signaling pathway known to promote tumor growth.

To reach their findings, the researchers used microrarray analysis to assess primary and metastasized tumors in mouse models of colorectal cancer.

When the mice were fed a high-fat diet, the growth of cancer stem cells in the colon increased. Studies have indicated that cancer stem cells are a key driver in the growth and metastasis of tumors.

On further investigation, the team found that blocking the JAK2-STAT3 cellular signaling pathway in the rodents reversed the increase in cancer stem cell growth triggered by a high-fat diet.

When analyzing the effects of a high-fat diet in colorectal cancer mouse models that were obesity-resistant, the researchers were able to replicate their findings.

Kalady says that this study is the first to demonstrate how a specific molecular pathway might mediate the link between a high-fat diet and colorectal cancer, a discovery that could yield new treatments for the disease.

Meanwhile, new research singles out a few key elements of the Mediterranean diet that are most important for colorectal health.

The benefits of the so-called Mediterranean diet have been hailed in the news over recent years. Now, new research looks closely at the elements of the diet that could help to prevent the risk of colorectal cancer.

Among many other benefits, the Mediterranean diet has been shown to lower the risk of colorectal cancer. But the specifics of this beneficial role have not been studied in depth. New research - presented at the ESMO 19th World Congress on Gastrointestinal Cancer, held in Barcelona, Spain - singles out the few components of the Mediterranean diet key for preventing colorectal cancer. The first author of the study is Naomi Fliss Isakov, Ph.D., of the Tel-Aviv Medical Center in Israel.

More specifically, the research looks at the link between the components of the diet taken both separately and in combination, as well as the risk of developing advanced colorectal polyps.

Colorectal cancer tends to develop from advanced polyps, or adenoma. However, the chances of polyps becoming malignant depend on various factors, including size, structure, and location.

The researchers defined adherence to the Mediterranean diet as an above-average consumption of fruit, vegetables, nuts, seeds, and whole grains, as well as fish and poultry.


A below-median intake of red meat, alcohol, and soft drinks was also considered to be a key component of the diet. A Mediterranean diet was also described as having "a high ratio of monounsaturated to saturated fatty acids."

Having compared individuals with polyp-free colonoscopies and those whose colonoscopy showed advanced polyps, the authors found a clear association between components of the Mediterranean diet and the risk of colorectal cancer.

People with advanced polyps reported consuming fewer elements of the Mediterranean diet. More specifically, the average was 1.9 Mediterranean diet components in the advanced polyps group, compared with 4.5 components in the polyp-free group.

Surprisingly, even two or three elements of the diet correlated with a 50 percent reduction in the risk of advanced polyps, compared with consuming no key components at all.

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