Impact of cyclin D1 A870G polymorphism in esophageal adenocarcinoma tumorigenesis

The dramatically increased incidence and poor survival rates of esophageal adenocarcinoma (EAC) underscore the need for novel targets useful for risk assessment and therapeutic intervention. Altered expression of cyclin D1 has been proposed as an early predictor for malignant transformation in EAC; however, the mechanisms underlying cyclin D1 deregulation have not been identified. A single nucleotide polymorphism, A870G, of the cyclin D1 gene has been associated with the preferential encoding of a protein with an extended half-life. We investigated the association of the cyclin D1 A870G polymorphism with cyclin D1 protein expression and clinical characteristics and outcome in 124 patients treated at our institution for EAC. Our results indicate that the cyclin D1 AA/AG genotype is associated with earlier age of cancer onset, cyclin D1 protein deregulation in the primary tumors, and increased frequency of distant metastasis. Our findings suggest that cyclin D1 status could be useful to assess risk of progression to EAC, and strategies directed to modulate cyclin D1 expression may prove useful for interventions to slow or interrupt the EAC tumorigenesis process.