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:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
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.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#566 Is Your Gut Leaking?
This week we're busting the human gut wide open with Dr. Alessio Fasano from the Center for Celiac Research and Treatment at Massachusetts General Hospital. Join host Anika Hazra for our discussion separating fact from fiction on the controversial topic of leaky gut syndrome. We cover everything from what causes a leaky gut to interpreting the results of a gut microbiome test! Related links: Center for Celiac Research and Treatment website and their YouTube channel
Now Playing: Radiolab

The Flag and the Fury
How do you actually make change in the world? For 126 years, Mississippi has had the Confederate battle flag on their state flag, and they were the last state in the nation where that emblem remained "officially" flying.  A few days ago, that flag came down. A few days before that, it coming down would have seemed impossible. We dive into the story behind this de-flagging: a journey involving a clash of histories, designs, families, and even cheerleading. This show is a collaboration with OSM Audio. Kiese Laymon's memoir Heavy is here. And the Hospitality Flag webpage is here.