Family history and genetics plays an important role as well, particularly in patients less than 50 years. Approximately 25% of CRC arise in patients with a family history of disease while 5% arise in the setting of an established familial syndrome (89). The genetic syndromes associated with CRC can be divided into the hereditary polyposis colon cancers (HPCC) and hereditary nonpolyposis colon cancers (HNPCC). Categories of HPCC include: (I) Familial adenomatous Inhibitors,research,lifescience,medical polyposis; (II) MUTYH-associated polyposis;

(III) hyperplastic polyposis syndrome; (IV) TGX-221 research buy Peutz-Jeghers syndrome; and (V) Juvenile polyposis syndrome (89). Of the polyposis CRC familial adenomatous polyposis (FAP) is the most common. FAP is an autosomal dominant disease with 100% penetrance. Patients with Inhibitors,research,lifescience,medical FAP develop hundreds to thousands of adenomatous colonic polyps starting in the second decade of life with a 100% risk

of CRC (89,90). Another category of HPCC is the MUTYH – associated polyposis, an autosomal recessive colon cancer syndrome which accounts for 0.5% to 1% of all CRC (91,92). Patients with MUTYH – associated Inhibitors,research,lifescience,medical polyposis may have zero to thousands of polyps like FAP, with an estimated lifetime risk of CRC around 80% (92). Hyperplastic polyposis syndrome (HPS) is characterized by the development of numerous, large hyperplastic and sessile serrated polyps, with a 35% to 54% prevalence of CRC development (93). Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disease characterized by the development of pigmented macules on lips, mucosa, hands and feet, along with development of hamartomatous polyps as well as cancers in the CRC, stomach, small

bowel, pancreas, breast, sex cord, Inhibitors,research,lifescience,medical uterus, cervix and skin. Patients with PJS have a 39% lifetime risk of CRC and 93% risk for any other malignancy (94). Juvenile polyposis syndrome Inhibitors,research,lifescience,medical (JPS) typically presents in childhood and has an associated 10-38% lifetime risk of developing colon cancer (95). Lynch syndrome/HNPCC is the most common autosomal dominant inherited colon cancer family syndrome responsible for 10% of colon cancer cases before the age of 50 years (96). The risk of CRC is related to the development of innumerable adenomas. Diagnosis of HNPCC is based on the Amsterdam criteria taking into account the extracolonic malignancies which are common in HNPCC involving the endometrium, Astemizole stomach, ovary, urinary collecting system, skin, pancreatic and biliary tract (97). Patients with HNPCC have a seven fold increased risk of CRC and present at least 20 years younger than the general population (98). The histopathologic types of CRC recognized by the World Health Organization include adenocarcinoma, mucinous adenocarcinoma, signet ring carcinoma, small cell carcinoma, adenosquamous carcinoma, squamous cell carcinoma and undifferentiated carcinoma.