National Cancer Institute®
Last Modified: October 1, 2002
UI - 12353948
AU - Calvert PM; Frucht H
TI - The genetics of colorectal cancer.
SO - Ann Intern Med 2002 Oct 1;137(7):603-12
AD - Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Colon cancer is a common disease that can be sporadic, familial, or inherited. Recent advances have contributed to the understanding of the molecular basis of these various patterns of colon cancer. Germline genetic mutations are the basis of inherited colon cancer syndromes; an accumulation of somatic mutations in a cell is the basis of sporadic colon cancer; and, in Ashkenazi Jewish persons, a mutation that was previously thought to be a polymorphism may cause familial colon cancer. Mutations of three different classes of genes have been described in colon cancer etiology: oncogenes, suppressor genes, and mismatch repair genes. Knowledge of many of the specific mutations responsible for colon carcinogenesis allows an understanding of the phenotypic manifestations observed and forms the basis of genetic testing for inherited disease. Although genetic testing is possible and available, it is only an adjunct to the clinical management of persons at risk for colon cancer and patients with colon cancer. As a result of advances in the understanding of the molecular causes of colon cancer and the availability of colon cancer screening methods such as colonoscopy, it should be possible to prevent the vast majority of colon cancer in our society. Practicing clinicians should recognize the patterns of clinical colon cancer, understand its causes, and be able to use genetic testing and endoscopic screening for prevention.
UI - 11862214
AU - Hamada F; Bienz M
TI - A Drosophila APC tumour suppressor homologue functions in cellular adhesion.
SO - Nat Cell Biol 2002 Mar;4(3):208-13
AD - MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
Adenomatous polyposis coli (APC) is an important tumour suppressor in the intestinal epithelium. Its function in reducing nuclear beta-catenin and T-cell factor (TCF)-mediated transcription is conserved from Drosophila to mammals. But APC proteins are also associated with the plasma membrane. Here, we show that mutational inactivation of Drosophila E-APC causes delocalization of Armadillo (the Drosophila beta-catenin) but not DE-cadherin from adhesive plasma membranes. Extensive gaps between these membranes are visible at the ultrastructural level. The oocyte is also mislocalized in E-APC mutant egg chambers, a phenotype that results from a failure of cadherin-based adhesion. These results indicate that Drosophila APC functions in cellular adhesion; these results could have implications for colorectal adenoma formation and tumour progression in humans.
UI - 12098745
AU - Nakayama T; Morishita T; Kamiya T
TI - Adenomatous polyposis coli gene as a gatekeeper.
SO - Rev Gastroenterol Peru 2002 Apr-Jun;22(2):164-7
AD - Department of Surgery, Shizuoka Red Cross Hospital, Shizuoka-shi, Japan.
The Adenomatous Polyposis Coli (APC) Gene is a tumor suppressor gene located in the chromosome 5q21. It has a sequence of 2843 amino acids and a weight of 312 kD. The mutation of the APC gene occurs at the early stages of most sporadic colorectal cancers; and up to 30% in familial adenomatous polyposis. The absence of APC will indicate the inadequate migration of colon mucous cells and its accumulation resulting in polyps formation, which determines a stage in carcinogenicity. An adequate study in prone groups may lead to chemoprophylaxis and/or early treatment of polyps.
UI - 8977766
AU - Bonneton C; Larue L; Thiery JP
TI - The APC gene product and colorectal carcinogenesis.
SO - C R Acad Sci III 1996 Oct;319(10):861-9
AD - UMR 144 du CNRS, Compartimentation et dynamique cellulaires, Paris, France.
The adenomatous polyposis coli (APC) gene has been found to be mutated during the development of sporadic colorectal tumours as well as in familial adenomatous polyposis patients (FAP), mutations being somatic or germinal respectively. The gene product is truncated in the carboxyterminal region but the role of the APC protein in tumorigenesis is not well understood. The purpose of this review is to reassess studies on the APC protein in an attempt to understand how the loss of its functions may cause or contribute to the development of carcinomas.
UI - 11702663
AU - Zheng S; Liu X; Cao J
TI - [N-actyltransferase2 polymorphism in recurrence of colorectal polyps and adenomas]
SO - Zhonghua Yi Xue Za Zhi 2001 Aug 10;81(15):907-9
AD - Cancer Institute, Zhejiang University, Hangzhou 310009, China.
OBJECTIVE: To observe the polymorphism of metabolizing enzyme N-actyltransferase 2 gene in populations with history of colorectal adenoma and polyp and to explore the relationship between NAT2 gene phenotype and colorectal cancer genetic susceptibility. METHODS: A cohort of 4,076 patients with history of colorectal adenoma or polyp was established Fifty-two cases were randomly selected from those with recurrence more than 2 times during the twenty years' follow-up. Fifty-two without recurrence were randomly selected as controls. DNA was isolated from the lymphocytes of peripheral blood of these 104 subjects. NAT2 polymorphism was detected by PCR-RFLP. RESULTS: The frequency of wild-type NAT2 (Wt/Wt) was significantly higher in control group (17/52, 32.7%) than in recurrence group (8/52, 15.4%) (P < 0.05). The frequency of heterogeneity type of NAT2 was significantly higher in recurrence group (40/52, 76.9%) than in control group (30/52, 57.7%) (P < 0.05). If OR of wild-type NAT2 (Wt/Wt) was 1, OR of Wt/M* genotype was 2.96 (95% CI: 1.091-8.009), and OR of M*/M* genotype was 2.125 (95% CI: 0.666-6.781). There was no difference of distribution between rapid enzyme type and slow enzyme type in the two groups. CONCLUSION: The frequency of wild-type NAT2 gene (Wt/Wt) is significantly higher in patients without recurrence of adenoma or polyp than in patients with recurrence. The frequency of heterogeneity genotype of NAT2 is significantly higher in patients with recurrence of adenoma or polyp than in those without recurrence. Wild-genotype (Wt/Wt) may be a protection factor in recurrence of colorectal adenomas. No difference can be seen between the distribution of rapid and slow enzyme types in these two groups.
UI - 11969232
AU - Tejpar S; Van Cutsem E
TI - Molecular and genetic defects in colorectal tumorigenesis.
SO - Best Pract Res Clin Gastroenterol 2002 Apr;16(2):171-85
AD - Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.
Colorectal cancers, whether sporadic or hereditary, are caused by a defined set of molecular events. There are at least two different pathogenetic pathways for colorectal cancer: the chromosomal instability pathway and the microsatellite instability pathway; the two major inherited syndromes, familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), are examples of these two mechanisms. These different pathways, however, converge on common pathological entities that have crucial functions in the regulation of normal crypt homeostasis. Preventive strategies aimed at reversing these changes, or therapeutic interventions targeting cell populations with these alterations, should be most efficacious. Genetic testing for inherited syndromes is now available and allows appropriate management of these disorders. Further insight into colorectal tumorigenesis pathways can lead to the development of useful prognostic indicators and target preventive and therapeutic strategies in the management of colorectal cancer. Copyright 2002 Elsevier Science Ltd.
UI - 12210511
AU - Barth AI; Nelson WJ
TI - What can humans learn from flies about adenomatous polyposis coli?
SO - Bioessays 2002 Sep;24(9):771-4
AD - Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305-5435, USA. email@example.com
Somatic or inherited mutations in the adenomatous polyposis coli (APC) gene are a frequent cause of colorectal cancer in humans. APC protein has an important tumor suppression function to reduce cellular levels of the signaling protein beta-catenin and, thereby, inhibit beta-catenin and T-cell-factor-mediated gene expression. In addition, APC protein binds to microtubules in vertebrate cells and localizes to actin-rich adherens junctions in epithelial cells of the fruit fly Drosophila (Fig. 1). Very little is known, however, about the function of these cytoskeletal associations. Recently, Hamada and Bienz have described a potential role for Drosophila E-APC in cellular adhesion, which offers new clues to APC function in embryonic development, and potentially colorectal adenoma formation and tumor progression in humans. Copyright 2002 Wiley Periodicals, Inc.
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