| Theme |
Precancerous Conditions and Cancer High-risk Lesions in the Colorectum |
| Title |
Hereditary Non-polyposis Colorectal Cancer (HNPCC) |
| Author |
Hiroyuki Yamamoto |
First Department of Internal Medicine, Sapporo Medical University School of Medicine |
| Author |
Hiroaki Taniguchi |
First Department of Internal Medicine, Sapporo Medical University School of Medicine |
| Author |
Tokuma Tanuma |
First Department of Internal Medicine, Sapporo Medical University School of Medicine |
| Author |
Yasutaka Sukawa |
First Department of Internal Medicine, Sapporo Medical University School of Medicine |
| Author |
Hiroaki Kunimoto |
First Department of Internal Medicine, Sapporo Medical University School of Medicine |
| Author |
Yasuhisa Shinomura |
First Department of Internal Medicine, Sapporo Medical University School of Medicine |
| [ Summary ] |
Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is best understood as a hereditary predisposition to malignancy caused by a germline mutation in a DNA mismatch repair (MMR) gene. Predisposed individuals have an increased lifetime risk of developing a variety of cancers including cancers of the colorectum, endometrium, and less frequently, cancers of the small bowel, stomach, urinary tract, ovaries and brain. HNPCC is characterized by early age of colorectal cancer (CRC) onset, proximal colonic cancer predilection, high risk of multiple CRCs, and increased risk for malignancy at certain extracolonic sites. DNA MMR deficiency results in a strong mutator phenotype and high-frequency microsatellite instability(MSI-H), which are the hallmarks of tumors arising within HNPCC. Inactivation of cancer-related genes, such as BAX, HDAC2, and TARBP2, due to frameshift mutations is assumed to be the driving force behind HNPCC. HNPCC is principally diagnosed based on the Amsterdam Criteria II (AC-II) in which gastric cancer is not considered to be HNPCC related. Therefore, the limitations of AC-II need to be recognized in clinical settings. In this regard, the revised Bethesda guidelines for testing CRCs for MSI are useful. BRAF V600E mutation analysis is a reliable, fast and low-cost strategy which simplifies genetic testing for HNPCC. Genetic analysis enables predictive testing of at-risk relatives and target surveillance in those found to be carriers. |