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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial adenomatous polyposis (FAP) is caused by germline mutations in the APC gene. This study included 71 Israeli families referred for molecular analysis of the APC gene. Analysis was performed by the protein truncation test (PTT) of exon 15, and if negative, by direct sequencing of exon 1 to 14. Mutations were found in 36 (50.7%) probands. Mutation detection rates depended on the pattern of referral, such that among the 40 probands referred from the Service for Hereditary Cancer the mutation detection rate was 70%, whereas among the 31 probands referred by other gastroenterologists detection rate was significantly lower (25.8%). Of the 36 mutations detected, 21 were within exon 15, 13 within exons 1 to 14 and 2 were newly-described splicing mutations in introns 9 and 14. A relatively high proportion of the mutations was detected in exon 9 (6/36), five of them newly described. Altogether, we describe here 17 new mutations. Within the two major ethnic groups in Israel, patients of Ashkenazi and non-Ashkenazi origin, there was no significant differences in the mutation detection rate or the distribution of mutations within the APC gene. No founder mutation was detected in any of these populations. Our data confirm that higher detection rates may be expected in patients referred by clinical services specializing in hereditary colon cancer. These results further underscore the importance of complete analysis of all exons and exon/intron boundaries, in order to achieve maximal detection rate in patients suspected of FAP.
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PMID:Molecular analysis of the APC gene in 71 Israeli families: 17 novel mutations. 1200 23

Only a small proportion of cancers result from familial cancer syndromes with Mendelian inheritance. Nonfamilial, 'sporadic' cancers, which represent most cancer cases, also have a significant hereditary component, but the genes involved have low penetrance and are extremely difficult to detect. Therefore, mapping and cloning of quantitative trait loci (QTLs) for cancer susceptibility in animals could help identify homologous genes in humans. Several cancer-susceptibility QTLs have been mapped in mice and rats, but none have been cloned so far. Here we report the positional cloning of the mouse gene Scc1 (Susceptibility to colon cancer 1) and the identification of Ptprj, encoding a receptor-type protein tyrosine phosphatase, as the underlying gene. In human colon, lung and breast cancers, we show frequent deletion of PTPRJ, allelic imbalance in loss of heterozygosity (LOH) and missense mutations. Our data suggest that PTPRJ is relevant to the development of several different human cancers.
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PMID:Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers. 1208 27

While the vast majority of cancers are believed to occur sporadically, most forms of cancer, both adult and paediatric, have a hereditary equivalent. In the case of adult malignancies, these include hereditary breast and ovarian cancer and syndromes such as the multiple endocrine neoplasias types 1 and 2 characterised by specific tumours of the endocrine gland system. In the case of paediatric malignancies, these include syndromes such as retinoblastoma and Wilms tumour. In a little over a single decade, we have seen a tremendous increase in the knowledge of the primary genetic basis of many of the familial cancer syndromes. The majority of familial syndromes are inherited as autosomal dominant traits including hereditary colon cancer and familial malignant melanoma, however, the genetics behind autosomal recessive disorders such as Bloom syndrome and Fanconi anaemia are also being elucidated. A third mode of inheritance less well understood in the setting of familial cancer is that of imprinting recently observed in a subset of families with inherited paraganglioma. In this review, we discuss 31 genes inherited in an autosomal dominant manner associated with 20 familial cancer syndromes. Genes inherited in an autosomal recessive manner linked to familial cancer syndromes are also discussed. The identification of genes associated with familial cancer syndromes has in some families enabled a 'molecular diagnosis' that complements clinical assessment and allows directed cancer surveillance for those individuals determined to be at-risk of disease.
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PMID:Genetic insights into familial cancers-- update and recent discoveries. 1217 30

Although several genes causing familial cancer syndromes have been identified, susceptibility to sporadic cancer remains unsolved. Animal experiments have demonstrated a large number of quantitative trait loci affecting cancer susceptibility. Previously, we described in mouse strain CcS-19/Dem five susceptibility to colon cancer (Scc) loci, Scc1-Scc5 controlling tumor numbers. In the present study, we performed an independent identical mouse cross using a distinct carcinogen, azoxymethane, to induce colon tumors. We confirmed all five originally described Scc loci and detected five additional new Scc loci; Scc11-Scc15. All these loci were detected in two-way interactions.
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PMID:Five new mouse susceptibility to colon cancer loci, Scc11-Scc15. 1456 56

While the I1307K APC mutation clearly confers an increased lifetime risk for colorectal cancer, there is a paucity of data on the natural history of colonic neoplasia in symptomatic and asymptomatic mutation carriers. In this study, 51 Jewish I1307K APC mutation carriers were identified in a high-risk familial cancer clinic over a 4-year period, of whom 29 (56.8%) (four males and 25 females) were successfully telephone interviewed for 0.5-5 years (mean 2.4 +/- 1.4) after initial genetic testing. Of these 29 cases, one individual was diagnosed with colon cancer at the age of 45 years, five had adenomatous polyps (mean number of polyps = 1.8), 11 had breast cancer (mean age at diagnosis 49.5 +/- 10.5 years), and 12 were asymptomatic, at the time of the testing. During the follow-up period, new colonic polyps were diagnosed in three mutation carriers, two with previously diagnosed colon cancer and polyps and only one of the asymptomatic mutation carriers, and two additional previously affected patients had new cancer diagnoses: gastric cancer and melanoma. From this descriptive study, it seems that the short-term risk for colonic polyps in I1307K APC mutation is low, primarily affecting patients with previously diagnosed colon tumors.
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PMID:The I1307K APC mutation in a high-risk clinic setting: a follow-up study. 1573 72

Four members of a family, thirteen subjects of which developed cancer for three consecutive generations were surgically treated in our Unit for colon cancer. It is well known to day that adenocarcinoma of the colon, as well as of other organs, has been proved to occur in certain families by a dominant trait, in the absence of any precancerous lesions. Due to this and because none of our patients has had any of the above mentioned lesions and because their tumors developed in the colon de novo, we have to accept that there is a hereditary predisposition in the development of familial cancer generally, which holds for our patients too. Because of a very high incidence of cancer, close follow-up of these families is recommended, that must start early and completed by chromosome and immunobiologic studies for all first, second and third degree relatives.
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PMID:Large bowel familiary cancer in patients without familiary polyposis. 1758 25

Germline TP53 mutations predispose to a rare familial cancer syndrome, the Li-Fraumeni Syndrome (LFS), characterized by the early onset of multiple cancers including childhood adrenocortical carcinomas, sarcomas and brain tumors, and breast and colon cancer in young adults. An identical germline mutation at codon 337 in TP53 (R337H) has been shown to be causally related to an increased risk of multiple cancers in unrelated subjects with familial cancer risk in Southern Brazil. Here we have assessed the prevalence of R337H in 750 healthy women participating in a community-based breast cancer screening program in the area of Porto Alegre. The mutant was detected in two participants (0.3%) who were fourth-degree relatives and reported a familial history of cancer at multiple sites that did not match classical criteria for LFS and its variants. Testing in additional family members detected the mutation in three subjects, one of whom developed breast cancer at the age of 36. These findings indicate that R337H may be a low penetrance mutant which predisposes to multiple cancers and occurs in the population of Southern Brazil at a frequency 10-20 times higher than other TP53 mutants commonly associated with LFS.
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PMID:Detection of R337H, a germline TP53 mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening program in Southern Brazil. 1824 85

Colon cancer, the third leading cause of mortality from cancer in the United States, afflicts about 150,000 patients annually. More than 10% of these patients exhibit familial clustering. The most common and well characterized of these familial colon cancer syndromes is hereditary nonpolyposis colon cancer syndrome (Lynch syndrome), which accounts for about 2% to 3% of all cases of colon cancer in the United States. We review the current knowledge of familial cancer syndromes, with an emphasis on Lynch syndrome and familial adenomatous polyposis.
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PMID:Syndromic colon cancer: lynch syndrome and familial adenomatous polyposis. 1831 39

As the molecular basis of disease continues to be elucidated, familial cancer syndromes, which consist of a range of neoplastic and non-neoplastic features, are emerging. The usual pathway of referral to a genetics clinic or familial cancer centre is via an oncologist, when high-risk features that suggest a possible hereditary basis for the presenting cancer are recognised. Traditionally, these high-risk features include more than two family members with similar cancers over two or more generations, a young age of onset, and more than one synchronous or metachronous tumour. These features are effective in ascertaining a substantial proportion of families with hereditary breast and ovarian cancer due to a BRCA mutation, or the more common bowel-cancer predisposition syndromes, such as hereditary non-polyposis colon cancer and familial adenomatous polyposis. However, there are a range of familial cancer syndromes that are not easily detected and that can remain undiagnosed when history and examination are not extended to include non-malignant features. The identification of cutaneous signs associated with rare familial-cancer syndromes provides individuals and their families with the opportunity to undertake early surveillance for malignant and non-malignant complications that might in time be shown to improve outcomes.
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PMID:Lessons from the skin--cutaneous features of familial cancer. 1845 57

Most genetically engineered mouse (GEM) models for colon cancer are based on tissuewide or germline gene modification, resulting in tumors predominantly of the small intestine. Several of these models involve modification of the adenomatous polyposis coli (Apc) gene and are excellent models for familial cancer predisposition syndromes. We have developed a stochastic somatic mutation model for sporadic colon cancer that presents with isolated primary tumors in the distal colon and recapitulates the entire adenoma-carcinoma-metastasis axis seen in human colon cancer. Using this model, we have analyzed tumors that are either solely mutant in the Apc gene or in combination with another colon cancer-associated mutant gene, the Kras G12D allele. Because of the restricted location in the distal colon, the natural history of the tumors can be analyzed by serial colonoscopy. As the mammalian target of rapamycin (mTOR) pathway is a critical component of the complex signaling network in colon cancer, we used this model to assess the efficacy of mTOR blockade through rapamycin treatment of mice with established tumors. After treatment, Apc mutant tumors were more than 80% smaller than control tumors. However, tumors that possessed both Apc and Kras mutations did not respond to rapamycin treatment. These studies suggest that mTOR inhibitors should be further explored as potential colorectal cancer therapies in patients whose tumors do not have activating mutations in KRAS.
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PMID:Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment. 2008 Jun 88


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