A 26-year-old healthy man comes to your clinic for an annual wellness examination. He does not take any medications. He smokes half pack of cigarettes daily. He tells you that his father died of colon cancer at the age of 45. He also has a 25-year-old cousin who recently had colonoscopy for rectal bleeding was found to have multiple polyps and is scheduled for total colectomy. Your patient wants to know if he can inherit colon cancer and if there is a way to find out if he is at risk. You talk to him about how some cancers can be caused by genetic mutations. For what genetic mutation is this patient at highest risk?
Familial adenomatous polyposis (FAP) is characterized by the appearance of thousands of adenomatous polyps throughout the large bowel. It is transmitted as an autosomal dominant trait. It is associated with a deletion in the long arm of chromosome 5, which contains the APC gene. The colonic polyps are usually evident by age 25. If untreated, patients usually develop colon cancer by the age of 40. Once multiple polyps are detected, patients should undergo a total colectomy, which is the primary therapy to prevent colon cancer. Current guidelines recommend that patients with a family history of FAP should have screening with flexible sigmoidoscopy or colonoscopy beginning at the age of 25, followed by annual screening until age 35. An alternative method for identifying carriers is testing peripheral blood mononuclear cell DNA for the presence of a mutated APC gene. The detection of this mutation can lead to a definitive diagnosis before the development of polyps. The MEN 1 gene is associated with multiple endocrine neoplasia type 1, which does not increase the risk of colon cancer. The RET gene is associated with multiple endocrine neoplasia type 2. The MSH gene is associated with hereditary nonpolyposis colon cancer (HNPCC), also known as Lynch syndrome. In contrast to FAP, patients with HNPCC or Lynch syndrome do not develop multiple polyps but instead develop only one or a few adenomas that rapidly progress to cancer. This condition is also strongly associated with ovarian and endometrial carcinoma. The BRCA gene is associated with familial breast and ovarian cancers.
MEN1
RET
APC
MSH
Oncology