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 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 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).
“This now needs to be tested in larger prospective studies, but it looks promising,” he said.
The analysis included 307 patients enrolled in a prospective case-control study designed to evaluate 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).
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).
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).
Other work presented by Dr. Casson's team—at both the Canadian Association of Thoracic Surgeons meeting and the World Congress of Gastroenterology—supports the hypothesis that a chronic inflammatory process is behind the progression from GERD to EACA.
The study 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%).
It also found nitrotyrosine expression present in 43% of EACA patients, compared with 22% and 24% of BE and GERD patients, respectively.
Nitric oxide damage has been implicated as a potential causative factor in p53 mutations, and the studies also found higher levels of these mutations in EACA patients, compared with BE and GERD patients.