The aim of this thesis was to gain better understanding of the etiology, the detection, and the palliative treatment of gastrointestinal cancer. We found HOX genes are mediators of (pre)malignant gastrointestinal lesions, vitamin D receptor polymorphisms and immunohistochemical biomarkers can be used to predict the risk of esophageal adenocarcinoma development, and palliative therapy modestly prolongs patient’s life and cost effectiveness of therapies can be assessed after phase II trials.