Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colorectal cancer (CRC) has a strong familial component. Candidate genes for colorectal cancer have been identified through mutations in four mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) and genes that are deleted or mutated in tumors (DCC, APC, and p53). Linkage analysis of candidate loci/regions was performed in 10 kindreds ascertained for common colorectal cancer from the Utah Population Database. Evidence for linkage to candidate genes was assessed using two- or three-point logarithm of the odds ratio scores with markers spanning the region of localization. One kindred is linked to hMSH2 and also fits the criteria for hereditary nonpolyposis colorectal cancer, having early age of onset and high penetrance for CRC. The remaining nine kindreds are unlinked to the candidate genes tested. These kindreds have a later age of onset and a lower penetrance than hereditary nonpolyposis colorectal cancer kindreds. these results indicate that further unmapped susceptibility loci may be responsible for much of the familial aggregation of CRC.
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PMID:Genetic heterogeneity and unmapped genes for colorectal cancer. 864 Aug 29

Research in hereditary forms of colorectal cancer (CRC) has increased almost logarithmically thanks in a major way to momentous discoveries in molecular genetics during the past decade. Between 10 and 20% of the total CRC burden is due to Mendelian-inherited CRC syndromes. The paradigm for hereditary CRC is familial adenomatous polyposis (FAP), wherein the APC germ-line mutation has been identified. This has contributed to the elucidation of genomic and clinical heterogeneity within the syndrome, wherein an attenuated form of FAP has been identified as a result of intragenic mutations within this large APC gene. The most common form of hereditary CRC is hereditary nonpolyposis colorectal cancer (HNPCC). Several mutator genes, namely hMSH2, hMLH1, hPMS1, hPMS2 and, more recently, hMSH6/GTBP, have been identified. These molecular genetic discoveries are providing new insights into the pathogenesis of CRC. Individuals within these kindreds who are harbingers of these germ-line mutations will benefit from screening and, one day, chemoprevention.
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PMID:Genetics of colonic cancer. 970 33

Familial cancers associated with genetic background are of the most intensively investigated diseases in recent years. The phenotype is apparent with most of these diseases and can easily be traced through family history. Induction in familial cancer appears, on current evidence, to be not different from that observed in sporadic cancer. The first suppressor gene Rb gene was cloned from retinoblastoma. There are two representative hereditary colorectal cancers: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). The gene responsible for FAP (APC gene) was cloned in 1991. The APC gene is a negative regulator of beta-catenin and is considered to play the role of gatekeeper in the adenoma carcinoma sequence. Thereafter a group of genes, human homologues of mismatch repair genes (hMSH2, hMLH1, hPMS1, hPMS2, hMSH6), have been identified as the genes responsible for HNPCC. These are called care taker genes, which serve to maintain genetic stability. Therefore, if one of those genes undergoes mutation, the rate of mutation increases significantly. It has only been in the last 20 years that familial cancer has become an important issue. In association with such advances, predictive testing can now be performed on at risk persons. Persons at risk can thus be accurately counseled and screened for early detection of disease.
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PMID:[Familial cancer: recent advances]. 1041 Jan 40

The discovery of genes responsible for inherited forms of colorectal cancer have the potential to improve cancer risk assessment and counseling. Germline mutations (nonsense, frameshift) of APC are associated with familial adenomatous polyposis, an autosomal dominant syndrome, clinically characterized by young onset, hundreds of adenomatous polyps in the colon, and increased risk for extracolonic tumors. Mutations in APC are also associated with forms of attenuated familial adenomatous polyposis. Germline mutations in five mismatch repair related genes (hMSH2, hMLH1, hMSH6, hPMS1, and hPMS2) cause hereditary nonpolyposis colorectal cancer and are associated with increased risk of somatic genetic alterations and high DNA microsatellite instability. Hereditary nonpolyposis colorectal cancer is characterized by young onset colorectal cancer, proximal colon location, and increased risk of extracolonic cancers. A missense mutation in APC (I1307K) is associated with some familial colorectal cancer in Ashkenazic Jews. For persons at risk for hereditary forms of colorectal cancer, testing algorithms and gene test interpretations depend on identification of the pedigree germline gene mutation. Careful evaluation of the kindred for characteristic aggregation of tumor types among affected individuals and the availability of affected persons for testing are important issues in implementing genetic testing and follow-up management. Case reports illustrate the importance of genetic counseling as a component of cancer genetic risk assessment. The genetic counseling process includes exploration of patient risk perception, sources of anxiety related to cancer risk, patient education (specific cancer-related issues, prevention/intervention options), discussion of possible gene test options, test limitations, and consequences of various gene test outcomes.
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PMID:Genetic testing and counseling for hereditary forms of colorectal cancer. 1063 Jan 80