MONTREAL — Genetic testing of patients with Barrett's esophagus to determine their risk for progression to esophageal adenocarcinoma might be a reasonable consideration in the near future, according to Alan G. Casson, M.B., professor of surgery at Dalhousie University in Halifax, N.S.
In a recently published paper that he presented at the annual meeting of the Canadian Association of Thoracic Surgeons, Dr. Casson showed that the CCND1 G870A polymorphism is found with increasing frequency through the chronic inflammation spectrum, from gastroesophageal reflux disease (GERD) through Barrett's esophagus (BE) and on to esophageal adenocarcinoma (EACA).
The CCND1 G870A polymorphism can be identified easily by blood testing.
“The contribution of this polymorphism to susceptibility of defined stages of progression to esophageal adenocarcinoma suggests [that] the incorporation of CCND1 genotype analysis in endoscopic Barrett surveillance programs may allow better stratification of individuals at increased risk for malignant progression,” he wrote (Cancer 2005;104:730–9).
“If you are a member of a population with this polymorphism, your chance of getting cancer is relatively higher. This now needs to be tested in larger prospective studies, but it looks promising,” he said in an interview.
The analysis included 307 patients enrolled in a prospective case-control study designed to evaluate lifestyle risk factors and molecular alterations in GERD (126 patients), BE (125), and EACA (56).
Compared with healthy, asymptomatic controls (95), all patients had elevated levels of the CCND1 A/A genotype, after adjustment for age and gender, Dr. Casson said. And the prevalence of this abnormality increased from GERD (odds ratio 2.8) through BE (OR 3.7) and EACA (OR 5.9).
“If an individual has this polymorphism, closer screening or surveillance would be warranted to detect early cancer,” he explained.
In the second part of the study, which was presented as an award-winning poster at the 13th World Congress of Gastroenterology, Dr. Casson's team identified obesity, smoking, and increased alcohol consumption as significant predictors of risk for progression of GERD and BE to EACA.
Obesity was identified as the main lifestyle risk factor for EACA (OR 4.67), followed by smoking (OR 3.86), whereas increased alcohol consumption was a risk factor for GERD (OR 2.69) and BE (OR 3.86).
“There has been a lot of controversy about the role of alcohol in esophageal cancer,” Dr. Casson said. “Although it is a well-documented risk factor for squamous esophageal cancer, its role has been less clear for adenocarcinomas. But we have shown that it is a significant risk factor.”
The study found that a diet high in vitamin C can decrease the risk of GERD (OR 0.4), BE (OR 0.44), and EACA (OR 0.2), and that multivitamin supplementation further reduced the risk of EACA (OR 0.17).
In another study, investigators found a progressive increase in levels of nitrotyrosine, a marker for nitric oxide-induced cellular damage, in esophageal tissue samples from patients with GERD (4%), BE (20%), and EACA (35%).