Study identifies 4 genetic variants linked to esophageal cancer and Barrett's esophagus

An international consortium co-led by researchers at Fred Hutchinson Cancer Research Center and the QIMR Berghofer Medical Research Institute in Australia has identified four genetic variants associated with an increased risk of esophageal cancer and its precursor, a condition called Barrett's esophagus.

The findings, by corresponding author Thomas L. Vaughan, M.D., M.P.H., a member of the Epidemiology Program in the Public Health Sciences Division at Fred Hutch, are published online ahead of the December print issue of Nature Genetics. Vaughan co-led the project with co-author David Whiteman, Ph.D., head of the Cancer Control Group at QIMR (formerly known as the Queensland Institute for Medical Research).

Both are members of the international Barrett's and Esophageal Adenocarcinoma Consortium, or BEACON, an open scientific forum for research into the causes and prevention of esophageal cancer and Barrett's esophagus that involves more than 40 scientists in North America, Europe and Australia.

"Epidemiologic findings, largely based on the work of BEACON investigators, clearly demonstrate that environmental factors such as obesity, gastroesophageal reflux , smoking and diet are largely responsible for the rapidly increasing incidence and mortality from esophageal adenocarconima," said Vaughan, who serves as BEACON's chair and is also a professor of epidemiology at the University of Washington School of Public Health. "However, a growing body of evidence also suggests an important role for inherited susceptibility."

To better understand the role of genetics in Barrett's and esophageal cancer, Vaughan and his BEACON colleagues pooled data and DNA specimens from 15 international studies conducted in the past 20 years to estimate the heritability of these conditions and identify genetic variants associated with increased risk. Altogether they gathered DNA samples and lifestyle risk-exposure data from more than 8,000 study participants, including about 5,500 with esophageal cancer or Barrett's esophagus and about 3,200 participants without these conditions who served as a comparison group.

The DNA samples were genotyped at Fred Hutch using a high-density array that allowed for the simultaneous and accurate assessment of more than 1 million genetic variants. To increase the statistical power of the study and its ability to identify potential causal genetic mutations, information on control subjects gleaned from public data repositories was added to the mix. The data analysis was conducted at the University of Washington in collaboration with the QIMR research group in Queensland.

After combing through all of the data, the researchers identified genetic variants at three locations - on chromosomes 3, 9 and 19 - as being significantly associated with esophageal adenocarcinoma and Barrett's esophagus. In addition, they found that a genetic variant on chromosome 16 that had been previously linked to Barrett's esophagus was also associated with an increased risk of esophageal adenocarcinoma.