stomach and intestines. This kind of cancer usually occurs in the appendix, small intestine, or rectum. Its presence is associated with an increased risk of cancers affecting the other parts of the digestive system. It is usually treated with surgery. Field defects A "field defect" or "field cancerization" is a region of tissue that precedes and predisposes to the development of cancer. Field defects occur in progression to gastrointestinal tract cancers. These field defects may contain visible gross manifestations, epigenetic alterations and/or mutations. Esophagus Adenocarcinomas of the esophagus tend to arise in a field defect called Barrett's esophagus, a red patch of tissue in the generally pink lower esophagus. A diagnosis of Barrett’s esophagus is confirmed by a metaplastic change of the esophageal mucosa from squamous to columnar mucosa with intestinal metaplasia. Barrett's esophagus is the dominant pre-malignant lesion of esophageal adenocarcinoma, and has prevalent epigenetic alterations. Esophageal squamous-cell carcinomas may occur as second primary tumors associated with head and neck cancer, due to field cancerization (i.e. a regional reaction to long-term carcinogenic exposure). A field defect associated with progression towards squamous cell carcinoma can be identified with epigenetic markers. Stomach Gastric cancer develops within areas (field defects) of the stomach with atrophic gastritis and intestinal metaplasia: these lesions represent the cancerization field in which (intestinal-type) gastric cancers develop. In one study, the field defect was clearly demonstrated in gastric carcinogenesis using miRNA high throughput data from normal gastric mucosa (from patients who had never had a gastric malignant neoplasm), non-tumor tissue adjacent to a gastric cancer, and gastric cancer tissue. Greater than five-fold reductions were found in four miRNAs in tumor-adjacent tissues and gastric cancers as compared to those miRNA levels in normal gastric tissues. Large intestine When a segment of the large intestine, containing a cancer, is removed, the area adjacent to the cancer (and removed with it) may show additional neoplasia in the form of polyps (see image). This is visual evidence of a field defect. Some of these polyps may be premalignant neoplastic tumors. As shown by Hofstad et al., when polyps are allowed to remain in the colon and are observed for three years, about 40% of polyps are seen to grow larger, likely progressing towards cancer. Luo et al. summarized the substantial body of evidence that field cancerization occurs in the colon, often due to aberrant DNA methylation. Etiology Bile acids are synthesized in