A 26-year-old woman is evaluated for intermittent abdominal discomfort, diarrhea, and melena. The patient undergoes colonoscopy followed by total colectomy due to significant colonic abnormalities. Representative colon findings are shown in the image below. Her sister, who has the same biological parents and has no symptoms, also undergoes screening colonoscopy and has similar findings. If left untreated, which of the following is the most likely lifetime risk of colon cancer in the patient's sister?

Question

A 26-year-old woman is evaluated for intermittent abdominal discomfort, diarrhea, and melena.  The patient undergoes colonoscopy followed by total colectomy due to significant colonic abnormalities.  Representative colon findings are shown in the image below.  Her sister, who has the same biological parents and has no symptoms, also undergoes screening colonoscopy and has similar findings.  If left untreated, which of the following is the most likely lifetime risk of colon cancer in the patient's sister?

Quizplus · Accepted Answer

11ec160b_393d_df3b_9249_e37cf76dfa05_MD0001_00 This patient and her sister have innumerable colonic polyps, raising strong suspicion for the autosomal dominant hereditary disorder familial adenomatous polyposis (FAP). Patients with this disorder develop hundreds or thousands of colonic polyps in the second or third decade of life. These polyps behave similarly to colonic polyps that form in patients who do not have FAP (spontaneous polyps): they typically grow over time, do not regress, and are associated with a progressive risk for high-grade dysplasia and transformation to invasive cancer as they enlarge. Because patients with FAP have innumerable polyps, the risk that one or more will transform into invasive colonic carcinoma is nearly 100%. Therefore, colectomy is generally recommended. FAP is caused by a germline mutation to the tumor suppressor gene adenomatous polyposis coli (APC). The APC gene encodes for a protein that destroys beta-catenin. Loss of the APC protein results in elevated beta-catenin levels, which stimulates a transcriptional activator that leads to proliferation of intestinal crypt cells (and the subsequent formation of polyps). Patients may also have extracolonic manifestations such as gastric or duodenal polyps, desmoid tumors, and brain cancer, but these manifestations have lower penetrance than colonic polyps. Loss of control of the APC pathway is a crucial first step in the development of both hereditary and sporadic forms of colon cancer. Nearly 80% of sporadic colon cancers have somatic mutations to both APC alleles; the remainder usually have activating mutations to the downstream products of this pathway. Educational objective: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by germline mutation to the tumor suppressor gene adenomatous polyposis coli. Patients with FAP develop hundreds or thousands of colonic polyps; lifetime risk of colon cancer is close to 100%. __________ References: Hereditary and familial colon cancer. (http://www.ncbi.nlm.nih.gov/pubmed/20420945)

A 26-Year-Old Woman Is Evaluated for Intermittent Abdominal Discomfort, Diarrhea