Prior studies by the applicants indicate that: (1) THDOC (tetrahydrodeoxycorticosterone), a normal component of human bile, is carcinogenic in the hamster embryo cell transformation (HECT) test; (2) in the gut 21-DOH (21-steroid dehydroxylase), synthesized exclusively by E. lentum and phenotypically similar organisms, metabolizes THDOC to the noncarcinogenic pregnanolone; and (3) normal subjects, patients with adenomatous polyps, and patients with carcinoma of the colon and rectum can be distinguished on the basis of their fecal concentration of E. lentum (and, therefore, 21-DOH activity). We propose to study the E. lentum (21-DOH) concentration in feces in: (a) normal (healthy) volunteers and a vegetarian population; (b) patients with nonGI malignancies; (c) patients with non-neoplastic colorectal diseases (ulcerative colitis, Crohn's colitis, diverticulitis); (d) patients with premalignant neoplasms (adenomatous polyps, villotubular and villous adenomas); and (e) patients with colorectal carcinoma. Patients in groups d and e will undergo repeat lifetime tests for 21-DOH activity and carcino-embryonic antigen (CEA), and colonoscopy at regular intervals. 16alpha-DOH activity will be assayed simultaneously in all fecal samples to assure the specificity of 21-DOH. In connection with this research, we will attempt to isolate THDOC from selected fecal specimens and to determine the fecal concentrations of this compound. These studies may provide a fecal marker for colorectal neoplasms and, therefore, a measure of the effectiveness of its surgical treatment (polypectomy, colon resection). The marker may also facilitate the identification of patients with new or recurrent neoplasms and identify patient groups at increased risk of colonic cancer. From a theoretical point of view, these studies may aid our understanding of the polyp-cancer sequence and identify for the first time a relationship between bacterial metabolism and colorectal cancer. (4)
| McSherry, C K; Cohen, B I; Bokkenheuser, V D et al. (1989) Effects of calcium and bile acid feeding on colon tumors in the rat. Cancer Res 49:6039-43 |
