Hereditary syndromes causing increased<unk>  formation include: * Familial adenomatous<unk> osis (FAP) * Hereditary nonpolyposis<unk>  cancer * Peutz–Jeghers syndrome * Juvenile<unk> osis syndrome Several genes have been associated with<unk> osis, such as GREM1, MSH3, MLH3, NTHL1, RNF43 and RPS20. Familial adenomatous<unk> osis Familial adenomatous<unk> osis (FAP) is a form of hereditary cancer syndrome involving the APC gene located on chromosome q521. The syndrome was first described in 1863 by Virchow on a 15-year-old boy with multiple<unk> s in his colon. The syndrome involves development of multiple<unk> s at an early age and those left untreated will all eventually develop cancer. The gene is expressed 100% in those with the mutation and it is autosomal dominant. 10% to 20% of patients have negative family history and acquire the syndrome from spontaneous germline mutation. The average age of newly diagnosed patient is 29 and the average age of newly discovered<unk>  cancer is 39. It is recommended that those affected undergo<unk>  cancer screening at younger age with treatment and prevention are surgical with removal of affected tissues. Hereditary nonpolyposis<unk>  cancer (Lynch Syndrome) Hereditary nonpolyposis<unk>  cancer (HNPCC, also known as Lynch syndrome) is a hereditary<unk>  cancer syndrome. It is the most common hereditary form of<unk>  cancer in the United States and accounts for about 3% of all cases of cancer. It was first recognized by Alder S. Warthin in 1885 at the University of Michigan. It was later further studied by Henry Lynch who recognized an autosomal dominant transmission pattern with those affected having relatively early onset of cancer (mean age 44 years), greater occurrence of proximal lesions, mostly mucinous or poorly differentiated adenocarcinoma, greater number of synchronous and metachronous cancer cells, and good outcome after surgical intervention. The Amsterdam Criteria was initially used to define Lynch syndrome before the underlying genetic mechanism had been worked out. The Criteria required that the patient has three family members all first-degree relatives with<unk>  cancer that involves at least two generations with at least one affected person being younger than 50 years of age when the diagnosis was made. The Amsterdam Criteria is too restrictive and was later expanded to include cancers of endometrial, ovarian, gastric, pancreatic, small intestinal, ureteral, and renal pelvic origin. The increased risk of cancer seen in patients with by the syndrome is associated with dysfunction of DNA repair mechanism. Molecular biologists have linked the syndrome to specific genes such as hMSH2, hMSH1, hMSH6, and hPMS2. Peutz–Jeghers syndrome Peutz–Jeghers syndrome is an autosomal dominant syndrome that presents with hamartomatous<unk> s, which are disorganized growth of tissues of the intestinal tract, and hyperpigmentation of the interlining of the mouth, lips and fingers. The syndrome was first noted in 1896 by Hutchinson, and later separately described by Peutz, and then again in 1940 by Jeghers. The syndrome is associated with malfunction of serine-threonine kinase 11 or STK 11 gene, and has a 2% to 10% increase in risk of developing cancer of the intestinal tract. The syndrome also causes increased risk of extraintestinal cancer such as that involving breast, ovary, cervix, fallopian tubes, thyroid, lung, gallbladder, bile ducts, pancreas, and testicles. The<unk> s often bleeds and may cause obstruction that would require surgery. Any<unk> s larger than 1.5 cm needs removal and patients should be monitored closely and screen every 2 years for malignancy. Juvenile<unk> osis syndrome Juvenile<unk> osis syndrome is an autosomal dominant syndrome characterized by increased risk of cancer of intestinal tract and extraintestinal cancer. It often presents with bleeding and obstruction of the intestinal tract along with low serum albumin due to protein loss in the intestine. The syndrome is linked to malfunction of SMAD4 a tumor suppression gene that is seen in 50% of cases. Individuals with multiple juvenile<unk> s have at least 10% chance of developing malignancy and should undergo abdominal colectomy with ileorectal anastomosis, and close monitoring via endoscopy of rectum. For individuals with few juvenile<unk> s, patients should undergo endoscopic<unk> ectomy.
Colorectal polyp
Colorectal adenoma
Anal dysplasia
Anorectal varices
Gastric varices
Anal fistula
Callous ulcer
Reactive gastropathy