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

A 74-year-old man with an occult carcinoma of the colon developed pigmentation of the mouth and penis typical of the Peutz-Jeghers syndrome as the first manifestation of bilateral diffuse uveal melanocytic proliferation. The simultaneous appearance of extraocular pigmented lesion and those in the uveal tract of both eyes of this patient provides further evidence that bilateral diffuse uveal melanocytic proliferation may be caused by activation of occult melanocytic naevus cells in response to either a hormone-producing carcinoma or to some other common oncogenic stimulus.
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PMID:Acquired pigmentation simulating Peutz-Jeghers syndrome: initial manifestation of diffuse uveal melanocytic proliferation. 175 69

Heritable and genetic factors pertinent to colon cancer can be divided into three categories: inherited syndromes, genetic epidemiology, and molecular genetics. Familial adenomatous polyposis (FAP) and Gardner syndrome (GS) are rare dominantly inherited syndromes characterized by hundreds to thousands of colonic adenomatous polyps. Colon cancer occurs at a young age in both diseases unless the colon is removed. Peutz-Jeghers syndrome and familial juvenile polyposis are inherited hamartomatous polyposis conditions with a less dramatic, but definite, increased risk for colon cancer. These four polyposis syndromes together account for less than 1% of cases of colon malignancy. Hereditary nonpolyposis colorectal cancer is a dominantly inherited form of colon cancer characterized by an early age of onset and a predilection for proximal colonic tumours. Multiple primary malignancies are frequently observed and one or several adenomatous polyps are often present in affected individuals; 4-6% of colon cancer cases occur in relationship to this syndrome. Genetic epidemiological studies have consistently shown that first-degree relatives of persons with colon cancer have a twofold to threefold increased risk of having colon malignancy. More recent studies have found a similar risk among relatives of those with adenomatous polyps. Studies of colon cancer and adenomatous polyps in pedigrees have further demonstrated that this familial clustering probably occurs on the basis of partially penetrant inherited susceptibilities. These inherited susceptibilities probably interact with environmental factors to give rise to polyp growth and finally colon cancer. Molecular studies have begun to elucidate the genetic mechanisms of colon cancer at the DNA level. The germinal mutation of FAP and GS has been localized to the long arm of chromosome 5. Tissue samples from "random" adenomatous polyps and colon cancers have shown frequent and specific acquired DNA sequence deletions on chromosomes 5, 17, and 18. Mutations and over-expression of the ras oncogene likewise have been observed in such tissues. The chromosome 5 defect in polyp and cancer tissues is probably at the same locus as the germinal mutation of FAP. There is evidence that this locus normally regulates expression of the c-myc oncogene, which in turn probably has a regulatory function in DNA replication. The chromosome 17 deletion is a mutation of the gene for the transformation-associated protein, p53. Appropriate screening starting at a relatively young age is necessary to prevent cancer in the inherited syndromes. Screening is also indicated in close relatives of those with nonsyndromic or common colon cancer in view of the moderately increased risk for colon cancer in this group.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Risk and surveillance of individuals with heritable factors for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer. 228 1

While the inheritance pattern of familial polyposis coli is established as an autosomal dominant pattern, the expression of the various extracolonic manifestations associated with the neoplastic polyposis is less well understood. The discrete polyp cancer syndrome may not be recognized unless both polyps and colon cancer are considered in the inheritance pattern. The hamartomatous polyps follow a Mendelian-dominant inheritance pattern for the Peutz-Jeghers syndrome, while the inheritance pattern for the juvenile polyposis syndromes is less clear. Cowden's disease appears in a Mendelian dominant pattern, but the occurrence of colonic polyps is less well documented. The ganglioneuromas follow a mendelian dominant inheritance pattern, while the relationship and occurrence of colonic polyps in association with Torre's syndrome is uncertain. The Mendelian dominant inheritance pattern for the cancer family syndrome is documented; the role of colon polyps in this syndrome is less well understood. A further understanding of the inheritance patterns of these various colon polyps will lead to more understanding of the basic disease and help in prevention and early detection for treatment and cure.
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PMID:Patterns of inheritance of colonic polyps. 303 91

Cases of familial polyposis coli and Peutz-Jeghers syndrome are reported for the first time in Ethiopia. One case seemed to have the defect as a new mutation in his gene while the other possibly inherited from his father. The one with polyposis coli had transmitted the disease to his offspring. This patient had total colectomy for prophylaxis against a potential carcinoma of the colon.
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PMID:Familial polyposis in two Ethiopians. 818 81

We analyzed somatic mutation and loss of heterozygosity (LOH) in the serine/threonine kinase 11 (STK11)/Peutz-Jeghers syndrome gene in 49 colorectal tumors in three different stages of a dysplasia-carcinoma sequence. We detected LOH in 10 of 19 (52.6%) informative colorectal cancers at loci D19S886 and/or D19S883, but no LOH was observed in 25 informative adenomas. We detected a total of 9 somatic mutations [7 of 13 (53.8%) left-sided colon cancers and 2 of 7 (28.6%) left-sided adenomas with high-grade dysplasia], but no mutations were detected in right-sided colon tumors. Of the nine mutations, one was a frameshift mutation (the same mutation detected in Peutz-Jeghers syndrome family previously), and the other eight were missense mutations. This results indicate that STK11 is a tumor suppressor gene and that genetic changes of STK11 play an important role in left-sided colon cancer carcinogenesis.
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PMID:Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers syndrome gene in left-sided colon cancer. 973 85

Studies on human cancer predisposition syndromes have contributed significantly to our understanding on tumor initiation and progression. Work performed on hereditary colon cancer has been particularly fruitful. Much of the molecular background of the various intestinal polyposis syndromes, such as familial adenomatous polyposis (FAP), juvenile polyposis, and Peutz-Jeghers syndrome, has been revealed, pinpointing several key cancer-associated genes. Studies on hereditary nonpolyposis colorectal cancer (HNPCC) have revealed a novel mechanism of tumorigenesis; genomic instability caused by defective DNA mismatch repair (MMR). Understanding the molecular background of these diseases helps us to understand tumor initiation in the affected individuals. Relatively little is known about the details of tumor progression in hereditary and sporadic neoplasia. Certain additional gene mutations can be associated with advancing stages of the disease, but the pace and tempo of the process have remained obscure. A high mutation rate in MMR-deficient tumors has provided a new approach in the analysis of human tumor dynamics. Microsatellite (MS) sequences are frequently mutated in MMR deficient tumors. The high mutation rate allows the use of microsatellite mutations as a tool for analyzing the past patterns of tumor progression. This approach is similar to the use of MS mutations in studying human evolution and migrations. Such tumor studies have revealed progression pathways that differ from the classic adenoma-cancer sequence. The reasons why and how molecular clocks may reveal something new about a well-studied problem are discussed.
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PMID:Genetic predisposition and somatic diversification in tumor development and progression. 1103 41

We experienced an unusual case of duodenal adenocarcinoma associated with Peutz-Jeghers syndrome (PJS). A 34-year-old woman was admitted to our hospital with abdominal pain. She had been diagnosed as having PJS at 21 years of age, based on the presence of mucocutaneous pigmentation of the lip and fingertips, and colonic hamartomatous polyps. Abdominal computed tomography revealed a tumor in the third portion of the duodenum extending into the pancreas head. As the tumor was pathologically determined to be adenocarcinoma at the time of surgery, pylorus-preserving pancreaticoduodenectomy was performed. We carried out molecular analyses of this patient to examine the pathway of carcinogenesis in PJS. The tumor did not show somatic mutation of the APC and K-ras genes, which is a critical step for the adenoma-carcinoma sequence in colon cancer. Importantly, a germline mutation of the STK11 gene was detected at codon 281 delC in exon 6. Moreover, the tumor showed loss of heterozygosity of the 19p marker near STK11 and somatic mutation of the p53 gene. These findings suggest that STK11 is a tumor suppressor gene regulating the development of hamartomas, and that somatic mutation of p53 subsequently promotes gastrointestinal cancer at a later stage in PJS.
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PMID:Duodenal cancer in a patient with Peutz-Jeghers syndrome: molecular analysis. 1205 37

Colorectal cancer is the second leading cause of cancer-related death in the United States. Although most colorectal cancers are sporadic, about 25% have a familial predisposition and 5% to 7% are hereditary and occur in genetically distinct high-risk families. Advances in treatment options and management of hereditary colorectal cancer syndromes that have occurred over the past years have been principally due to advances in the understanding of the genetics of these syndromes and in additional options for testing. This has led to the possibility of preclinical diagnosis and early surveillance and treatment. In addition, improvements in medical and surgical management have also occurred. This article focuses on four hereditary colon cancer syndromes: familial adenomatous polyposis, hereditary non-polyposis colorectal cancer, juvenile polyposis syndrome, and Peutz-Jeghers syndrome.
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PMID:Treatment of Hereditary Colorectal Cancer Syndromes. 1514 83

Hereditary colorectal cancer syndromes are classified according to the presence of unusually large number of adenomatous or hamartomatous polyps, or their absence. The latter category includes hereditary non-polyposis colorectal cancer (Lynch syndrome) and its variants Muir-Torre and Turcot's syndromes. Adenomatous polyposis syndromes include familial adenomatous polyposis (FAP) and its variants, and the recently identified MYH- (mutY homolog)-associated polyposis. Hamartomatous polyposis syndromes include juvenile polyposis, Peutz-Jeghers syndrome, and Cowden syndrome, which is now included within the broader category 'PTEN (phosphatase and tensin homolog) hamartoma tumour syndrome'. Other syndromes such as the 'hereditary breast and colon cancer' and 'familial colorectal cancer' are not yet fully characterized. This review addresses the molecular basis of these syndromes with particular reference to the recent advances in this rapidly progressive field and the applications of such knowledge in diagnosis and management.
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PMID:Molecular basis and diagnostics of hereditary colorectal cancers. 1547 12

Inherited forms of gastrointestinal cancer have been a major focus of study and advancement over the past decade. Familial adenomatous polyposis and hereditary nonpolyposis colon cancer are the two most common heritable colon cancer syndromes. Inherited polyposis syndromes are characterized by the dominant type of polyp (whether adenomatous or hamartomatous) present and by the polyp's location within the gastrointestinal tract. The hamartomatous polyposis syndromes are characterized by an overgrowth of cells native to the area in which they normally occur. They represent a small but appreciable number of the gastrointestinal inherited cancer predisposition syndromes; it is now known that many of these syndromes carry a substantial risk for developing colon cancer as well as other gastrointestinal and pancreatic cancers. Patients afflicted with these syndromes are also at significant risk for extraintestinal malignancies. Seven inherited hamartomatous polyposis syndromes have been described: familial juvenile polyposis syndrome, Cowden's syndrome, Bannayan-Ruvalcaba-Riley syndrome, Peutz-Jeghers syndrome, basal cell nevus syndrome, neurofibromatosis 1, and multiple endocrine neoplasia syndrome 2B. Hereditary mixed polyposis syndrome is a variant of juvenile polyposis characterized by both hamartomatous and adenomatous polyps. The hamartomatous syndromes occur at approximately 1/10th the frequency of the adenomatous syndromes and account for <1% of colorectal cancer in Northern America. While the diagnosis of these inherited syndromes is primarily clinical, genetic testing is now available for all six syndromes. However, there are a significant number of spontaneous mutations seen in each of the syndromes. The management of these patients necessitates a coordinated multidisciplinary approach. The purpose of this review is to characterize the clinical and pathological features of these syndromes and to review the targets of cancer surveillance. The molecular alterations responsible for the inherited hamartomatous polyposis syndromes will also be discussed.
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PMID:The hamartomatous polyposis syndromes: a clinical and molecular review. 1566 10


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