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Gene Changes Risk of Esophageal Cancer

CancerWise - January 2009

Variations in a common gene pathway may affect the risk of esophageal cancer, a dangerous type of cancer that is becoming more common.

This is the first study to look at the link between genes related to microRNAs (miRNAs) and esophageal cancer. Scientists from MD Anderson published their results in the November issue of Cancer Prevention Research, a journal of the American Association of Cancer Research.

Significance of results

Cancer of the esophagus ranks sixth in cancer-related deaths worldwide, and the number of cases is increasing. According to the American Cancer Society, more than 16,000 people will be diagnosed and more than 14,000 people will die of the disease in the United States this year.

Major risk factors for esophageal cancer include tobacco smoking, alcohol drinking and reflux disease. The high incidence of these risk factors in the general population and the rare occurrence of the disease gave researchers a clue there might be a genetic connection.

Background

"Previous research has shown miRNAs control approximately one-third of human genes and may play a part in cancer risk," says the study's lead author, Xifeng Wu, M.D., Ph.D., professor in the Department of Epidemiology at M. D. Anderson. "But whether genetic variants of miRNA-related genes influence esophageal cancer has largely remained unknown."

Research methods

Researchers recruited 346 people who were newly diagnosed with esophageal cancer at M. D. Anderson. They matched them by age, gender and ethnicity to 346 people without cancer.

Only results for Caucasians were reported because of the low numbers of other races that enrolled. While patients tended to be smokers and have higher body mass index (BMI), there was no difference between the two groups in alcohol consumption.

To examine the potential roles of miRNA variations in esophageal cancer, researchers looked at the relationships among 41 single-nucleotide polymorphisms (SNPs) in 26 miRNA-related genes and the risk of esophageal cancer. SNPs are places in the human genome that vary by a single DNA chemical building block or nucleotide.

Primary results

Seven genotypes were associated significantly with esophageal cancer risk, and four more showed at least a borderline significance. The risk of esophageal cancer became higher when the number of unfavorable genotypes present increased.

"This research showed not only that a single gene contributes to the risk of esophageal cancer but more important, that the joint effect of several genetic elements can increase risk," says the study's first author, Yuanqing Ye, Ph.D., instructor in the Department of Epidemiology at M. D. Anderson.

Additional results

One of the most notable findings was an SNP in the mir423 region, which was associated with a significantly lower esophageal cancer risk. The protective effect was significant for smokers and nonsmokers 64 years old and younger, but not for older subjects.

Mir423 also is found in leukemia cells and is altered significantly in other diseases including heart disease and Alzheimer's disease.

What’s next?

Future large-scale, multicenter studies are necessary to confirm these findings, Wu says.

"Our ultimate goal is to construct a comprehensive risk prediction model that includes not only genetic factors, but epidemiological and clinical variables as well, in hopes of predicting the probability of developing esophageal cancer in the general population."

— Adapted by Dawn Dorsey from an M. D. Anderson news release

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© 2014 The University of Texas MD Anderson Cancer Center