Related Experiment Video
Updated: Jun 10, 2026
28:15
Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 29, 2010
Inherited susceptibility to colorectal cancer
1Department of Medicine and Division of Genetics, University of Rochester, Rochester, New York 14642, USA. peter_rowley@urmc.rochester.edu
Annual Review of Medicine
|January 22, 2005
Summary
Identifying genetic mutations for familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) is crucial for early cancer detection. Genetic testing improves surveillance compliance and reduces mortality for these inherited cancer syndromes.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) are principal Mendelian disorders predisposing to colorectal cancer.
- FAP results from APC gene mutations, while HNPCC involves mutations in mismatch repair genes.
- Early identification is critical as these conditions lead to approximately 80% risk of colon cancer with early onset.
Purpose of the Study:
- To highlight the importance of identifying individuals with FAP and HNPCC.
- To discuss the benefits of genetic testing for these hereditary colorectal cancer syndromes.
- To review current testing methodologies and their efficacy.
Main Methods:
- Protein truncation testing for FAP mutations.
- Microsatellite instability testing for HNPCC.
- Analysis of MLH1, MSH2, or MSH6 mutations in colorectal cancer patients with high microsatellite instability.
Main Results:
- Protein truncation testing identifies the majority of FAP mutations.
- Microsatellite instability testing detects 80%-95% of HNPCC cases.
- A U.S. study found 12% of colorectal cancers exhibit high microsatellite instability, with 25% of those having detectable MLH1, MSH2, or MSH6 mutations.
Conclusions:
- Genetic identification of FAP and HNPCC enables targeted surveillance and early polyp detection.
- Testing can significantly reduce colorectal cancer mortality and provide reassurance to at-risk families.
- Early diagnosis facilitates cascade testing within families, optimizing resource allocation for surveillance.
Related Concept Videos
01:35Pedigree Analysis
Overview
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
02:59Cancer Prevention
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:25Inflammatory Bowel Disease III: Crohn's Disease
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...