Nav: Home

Genome offers clues to esophageal cancer disparity

December 20, 2018

Dec. 20, 2018 -

A genomic duplication may help explain why esophageal adenocarcinoma is much more common in Caucasians and presents a potential target for prevention

ANN ARBOR, Michigan -- A change in the genome of Caucasians could explain much-higher rates of the most common type of esophageal cancer in this population, a new study finds. It suggests a possible target for prevention strategies, which preliminary work suggests could involve flavonoids derived from cranberries.

"We've known for a long time that esophageal adenocarcinoma primarily affects Caucasians and very rarely affects African-Americans," says David G. Beer, Ph.D., the John A. and Carla S. Klein professor of thoracic surgery and professor of radiation oncology at Michigan Medicine.

"We wanted to see if African-Americans have something genetic that's protective. If we understand why people have low risk, that can lead to understanding how to prevent cancer in those at high risk."

About 17,290 Americans will be diagnosed with esophageal cancer this year. Adenocarcinoma represents about two-thirds of cases but is rarely seen in African-Americans.

In the study, published in Gastroenterology, researchers examined tissue samples from African Americans and European Americans, including both those with esophageal adenocarcinoma and those without. They measured gene expression and protein levels and found a difference in the enzyme called GSTT2. This was significantly higher in African-Americans compared to Caucasians.

Researchers found Caucasians have a duplication on a portion of the genome that appears to reduce the expression of GSTT2. This enzyme protects cells against oxidative damage, such as the type caused by reflux, a key risk factor for esophageal adenocarcinoma.

They confirmed the initial findings by looking at expression and sequencing data from the 1000 Genomes Project, an international initiative that used genomic sequencing to provide a comprehensive view of human genetic variation. This data reinforced that populations from Africa or African descent had the non-duplicating genome, while all other populations around the world had the duplication.

"The risk factors for esophageal cancer such as obesity and reflux happen at the same rate for African-Americans and Caucasians. But African-Americans are not getting cancer," Beer says. "We see the highest risk of cancer in people who have this genomic duplication plus obesity. It's not just the presence of the duplication but these other factors contributing to the damage."

Rates of esophageal adenocarcinoma have increased 600 percent over the last three decades, caused by a rise in obesity and gastroesophageal reflux disease, or GERD. The other type of esophageal cancer, squamous cell carcinoma, is more frequently seen in African-Americans.

The researchers used cell lines and a rat model to recreate low levels of GSTT2. They saw more damage in these cells, compared to those expressing high levels of GSTT2.

Next, they used a cranberry proanthocyanidin extract and found it reduced levels of DNA damage in the esophagi of rats exposed to reflux. This suggests potential for preventing esophageal adenocarcinoma.

"They key with esophageal cancer is to prevent it. Many people don't know they have the disease until it's too late to treat it effectively," Beer says.

Researchers are considering a clinical trial to test using flavonoids derived from cranberries as a chemoprevention agent. However, more research is needed to understand appropriate dose and potential side effects.
-end-
Additional authors: Daysha Ferrer-Torres, Derek J. Nancarrow, Hannah Steinberg, Zhuwen Wang, Rork Kuick, Katherine M. Weh, Ryan E. Mills, Dipankar Ray, Paramita Ray, Jules Lin, Andrew C. Chang, Rishindra M. Reddy, Mark B. Orringer, Marcia I. Canto, Nicholas J. Shaheen, Laura A. Kresty, Amitabh Chak, Thomas D. Wang, Joel H. Rubenstein

Funding: National Cancer Institute grants CA163059, CA967622, CA200113, CA009676, CA046592, CA158319; John and Carla Klein family research fund

Disclosure: None

Reference:Gastroenterology, doi: 10.1053/j.gastro.2018.12.004, published online Dec. 19, 2018

Resources:

University of Michigan Rogel Cancer Center, http://www.rogelcancercenter.org
Michigan Health Lab, http://www.MichiganHealthLab.org
Michigan Medicine Cancer AnswerLine, 800-865-1125

Michigan Medicine - University of Michigan

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...