Hereditary syndromes cause approximately 5 to 15% of overall colorectal cancer (CRC) cases. Hereditary CRC is conventionally divided into two major categories: hereditary non-polyposis colorectal cancer (HNPCC) and those related to polyposis syndromes including familial adenomatous polyposis (FAP), Peutz-Jegher syndrome (PJS), and juvenile polyposis (JP). The screening for the cancer and methods of treatment applied to patients with hereditary CRC are quite different from those applied to the general population. The genes responsible for these syndromes has recently identified, as a result, genetic testing has become the most important determining factor in clinical decisions. Germ-line mutation of the APC gene induces FAP, an autosomal dominant disorder, characterized by the development of hundreds to thousands of colonic adenomas. CRC appears in almost all affected individuals by the time they are 50 years of age. An affected individual should undergo colectomy by his/her late teens. Furthermore, according to the findings of genetic testing, at-risk family members also need endoscopic surveillance and surgery. Recently, a mutation on the MYH gene is increasingly being investigated in patients with multiple polyps, and autosomal recessive MYH polyposis is considered to be a new category of polyposis. More common than FAP, HNPCC is caused by germ-line mutations in DNA mismatch repair genes, mainly MLH1 and MSH2. Although there is no polyposis, polyps seem to be more villous and dysplastic and appear to grow rapidly into CRCs. The aggregate lifetime risk of CRC is about 80% for mutation carriers. The risk for other types of cancer, such as endometrial, ovarian, small bowel, and transitional cell cancer, is also increased. The Amsterdam criteria and Bethesda guidelines are the best-known tools for diagnosis and genetic testing, and colectomy followed by endoscopic follow-up is the standard treatment. PJS and JP are reported to be characterized by hamartomatous polyps throughout the GI tract and germ-line mutations in the STK11 gene (PJS) and the DPC4/BMPR1A gene (JP).
Adenomatous Polyposis Coli/*genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis/*genetics ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Intestinal Polyposis/diagnosis/*genetics ; Peutz-Jeghers Syndrome/diagnosis/*genetics

Adenomatous Polyposis Coli ; genetics ; pathology ; Colonic Neoplasms ; classification ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; DNA Glycosylases ; metabolism ; Humans ; Intestinal Polyps ; pathology ; Lymphatic Metastasis ; Neoplasm Staging ; Neuroendocrine Tumors ; classification ; pathology ; Precancerous Conditions ; pathology ; Rectal Neoplasms ; classification ; genetics ; pathology ; World Health Organization