A recently published study by scientists at Australia’s QIMR Berghofer Medical Research Institute could have a significant 
impact on the study of esophageal adenocarcinoma, a rare but lethal form of cancer.
Along with esophageal cancer, the study looked at two other conditions that often are overlapping or related – gastroesophageal reflux disease, known more commonly as GERD, and Barrett’s esophagus. GERD is characterized by food and stomach acid flowing back up into the food pipe. Barrett’s esophagus is a complication caused by GERD in which the tissue lining the esophagus changes to resemble the lining of the intestines.
Both GERD and Barrett’s esophagus are considered key risk factors for developing esophageal cancer.
Lead by Puya Gharahkhani and Stuart Macgregor, at the QIMR Berghofer Medical Research Institute in Australia, the new study offers the first evidence for a polygenic basis for GERD, the researchers said.
The research also for the first time found evidence for an overlap in the genetic variants associated with all three conditions. The overlap appears to involve a large number of variants with a small effect size rather than a small number of variants with large effects. The identification of a shared genetic background for GERD, Barrett’s esophagus, and esophageal cancer may have clinical implications for finding treatments for these diseases.
Along with work from 23andMe scientists and data from more than 50,000 23andMe customers who consented to research, the study included data and contributions from researchers at VU University Amsterdam in the Netherlands, the Barrett’s and Esophageal Adenocarcinoma Consortium, and the Fred Hutchinson Cancer Research Center in Seattle.
The study included more than 8,000 23andMe customers with GERD, who consented to research and another 43,000 without the condition who were used as controls and also consented to research.
The condition is the strongest known risk factor for esophageal cancer. Although this form of cancer is rare – a lifetime risk of less than 1 percent for the general population – it has a very high mortality rate with fewer than 20 percent of those diagnosed surviving longer than five years. Because both GERD and Barrett’s are indicators for this deadly cancer, better understanding of the conditions and how they may overlap could lead to new insights into the condition and ultimately new therapies.
Although previous studies have found a handful of genetic variants associated with both esophageal cancer and Barrett’s esophagus, up until now researchers have not been able to find variants associated with GERD.
This is the first time researchers have shown a polygenic association with GERD, finding that the top 1 percent of genetic variants associated with GERD in one research cohort could be used collectively to predict the risk of GERD among another cohort, even though no individual variant could be definitively associated with GERD.
The researchers in this study believe that their work shows that combining data from these three conditions – GERD, Barrett’s esophagus, and esophageal cancer – in larger numbers will ultimately help identify specific genetic variants associated with these conditions. Ultimately they hope that this research could lead to breakthroughs and new treatments for three overlapping conditions.