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

Retinoblastoma (RB) and the familial adenomatous polyposis/colorectal cancer (FAP/CRC) complex provide well-characterised examples of multistage carcinogenesis and inheritance of a predisposition to cancer. Retinoblastoma appears to conform to the simple two-step model first proposed by Knudson. The gene responsible for RB, now called Rb1, has been located in chromosome region 13q14. The Rb1 gene has been cloned and subjected to extensive analysis. It is probable that the Rb1 gene product has a role in the regulation of transcription. The familial form of RB occurs as the result of a germline mutation of one of the copies of the Rb1 gene. Colorectal cancer, in contrast, appears to be the result of four or five steps involving both activation of oncogenes and inactivation of antioncogenes. The FAP gene has been located in chromosome region 5q21 by genetic linkage, and a candidate gene, MCC (mutated in colon cancer), has been cloned. Other mutations in previously-identified genes that have been identified as important in the genesis of CRC include the activation of p53 and of Ki-ras. A gene lying in chromosome region 18q which is deleted in colorectal cancer, and hence named DCC has been cloned. Its protein product has sequence homology to neural cell adhesion molecules and other related cell-surface glycoproteins. Delineation of the genes involved in the development of tumours such as RB and CRC provides insight into the mechanisms by which sequential mutations result in carcinogenesis.
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PMID:Multistage carcinogenesis in paediatric and adult cancers. 131 30

We report a male Japanese with corticotropin (ACTH)-independent macronodular adrenocortical hyperplasia (AIMAH) associated with multiple colon adenomas/carcinomas. The plasma cortisol level was elevated with no diurnal rhythm and was not suppressed with dexamethasone. Basal plasma ACTH was unmeasurable but subnormally increased after administration of metyrapone or corticotropin releasing hormone. Both adrenals were resected and weighed 90g; the histopathologic findings were similar to those of AIMAH as previously reported. At least 21 colon lesions which were adenomas or carcinomas, were resected endoscopically or surgically. This is the second reported case of the association of AIMAH with multiple colon polyps. An APC gene point mutation was detected in the colon cancer tissue by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP)/direct sequencing analysis at the putative splice acceptor site consensus sequence. However, no abnormality of APC gene was detected in the adrenocortical hyperplastic tissue. The possible etiological coexistence of these two diseases is discussed.
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PMID:Adrenocorticotropin-independent macronodular adrenocortical hyperplasia associated with multiple colon adenomas/carcinomas which showed a point mutation in the APC gene. 926 Jul 67

Epidemiological studies on risk factors for CRC have focused mainly on diet. In any case, the results of these studies show several inconsistencies, except for the beneficial role of high intake of vegetables and, to some lesser extent, of fruit. Weight and height have also been studied, partly because they reflect the balance between energy intake and expenditure in different age periods. Energy intake, body size and physical activity will be reviewed in this paper focusing mostly on recent data coming from Italian, English and Scandinavian studies. Overweight has long been recognized as a risk factor for hormone related and other cancers and this is confirmed not simply from case-control studies but from large cohort studies as well. The major findings of recent Italian studies are that excessive weight at various ages predicts colorectal cancer risk in men while in women, abdominal obesity, as indicated by a high WHR, represents a more reliable risk indicator. If all men could reduce their BMI below 25, about 9% of male colorectal cancer might be avoided in Italy. A decrease of WHR below 0.82 might reduce colorectal cancer in women by 19%. In addition, the epidemiological evidence consistently shows that physical activity reduces the risk of colon cancer. On the contrary, evidence on rectal cancer is less impressive. Some uncertainty still exists in relation to the intensity and duration of physical activity. In conclusion, body size control along all life and physical activity represent important factors to prevent colon cancer and a wide range of chronic conditions. Therefore, strategies to favour these goals through counselling from health-care providers, regulatory changes and programs aimed at individuals and communities should be implemented.
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PMID:Energy intake, overweight, physical exercise and colorectal cancer risk. 1077 19

The most common form of hereditary CRC is hereditary non-polyposis colorectal cancer (HNPCC), several mutator genes have been identified in this syndrome. The molecular genetic discoveries are providing news insights into the pathogenesis of CRC. The CRC in Lynch syndrome shows microsatellite instability and it also shows a special histology now referred to as an undifferentiated medullary or solid cribriform carcinoma. This histology is uncommon in various populations. In addition CRC in HNPCC shows an excess of mucoid features as well as peritumoral lymphocyte infiltration and Crohn-like reaction. It is very important to make a diagnosis based on the natural history features of a particular cancer syndrome in combination with a well orchestrated family history. We report the case of a 44 year old man with colon cancer and adenomatous polyps, without family history of adenomatous polyps but with familial antecedent of colon cancer in his father, with a suspicion of Lynch syndrome.
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PMID:[Hereditary familial non polypoid colorectal cancer]. 1137 Jan 76

MMR gene mutations and MSI are not found in all clinically diagnosed HNPCC families. We evaluated whether MMR genotyping and tumor MSI analysis could identify distinct clinical subgroups among HNPCC families. Twenty-nine clinical HNPCC families were divided into 3 groups: A, families with hMLH1 or hMSH2 gene mutations; B, MMR gene mutations not present but MSI present in at least 50% of tumors tested; C, mutational and MSI analyses negative. We evaluated tumor spectrum, age at onset, risk of cancer in the follow-up and survival for CRC in the 3 groups. Tumors of the target organs in HNPCC (colon and rectum, endometrium, ovary, small bowel, stomach, renal pelvis and ureter) were more frequent in the first 2 groups than in the latter. Colon cancer was more frequently located in the proximal colon and showed an earlier age at onset in families with MMR gene mutation or with MSI than in families with stable tumors. Comparing the occurrence of tumors in the follow-up, in the first 2 groups patients younger than 50 years had a higher RR, which was particularly marked for CRC (RR = 18.6 for group A vs. group C, RR = 16.7 for group B vs. group C). CRC patients in the first 2 groups had a better clinical prognosis. The results of molecular analysis could distinguish, within clinically defined HNPCC families, different subgroups to which specific programs of surveillance could be addressed.
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PMID:Clinical and biologic heterogeneity of hereditary nonpolyposis colorectal cancer. 1149 33

The primary treatment of resectable CRC is surgical resection. Postoperative adjuvant therapies are recommended when lymph node metastases are found (stage III). There is evidence that about 20% of node negative CRC cases (stage II) are understaged, i.e., they are actually node positive (stage III). New intraoperative procedures (lymphatic mapping and sentinel node identification) that are able to detect occult macro- and micrometastases. Molecular assessment of nodal disease should improve the current staging criteria for colon cancer and could influence recommendation for adjuvant treatment.
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PMID:Lymphatic mapping and sentinel node identification for colorectal cancer. 1177 43

Hereditary non-polyposis colorectal cancer (HNPCC), the most common hereditary colon cancer syndrome, is a dominant disorder caused by germline defects in mismatch repair (MMR) genes. Identification of MMR gene mutations can have direct clinical implications in counseling and management of HNPCC families. We screened 44 HNPCC and 97 suspected HNPCC Korean families for germline mutations in three MMR genes: MLH1, MSH2 and MSH6. We identified twelve novel mutations: nine in MLH1(c.632_633insT, c.808_811delACTT, c.845C>G, c.1625A>C, c.1730+1delG, c.1907T>C, c.1918C>T, c.2104-2A>G and c.2170T>A), two in MSH2 (c.1886A>G, c.1316_1318delCCT) and one in MSH6 (c.3488A>T). In addition, two statically significant cSNPs in MLH1: c.1128T>C ( p=0.008 in HNPCC and p=0.037 in early-onset CRC) and c.2168C>A ( p<0.001 in HNPCC). Interestingly, the most frequent mutation, c.1757_1758insC in MLH1, was a founder mutation inherited from a common Korean ancestor.
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PMID:Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families. 1536 95

The aim of the work was to study the effects of changes in the location of E-cadherin from membrane to cytoplasm and the appearance of metastases and recurrence in patients with colon cancer of pT1 grade. The study group consisted of 34 patients with colon cancer. The material was fixed in 10% buffered, directly following surgery, fixed in fonnaldehyde and embedded in paraffin blocks by a standard method. Immunohistochemical reactions were performed, using monoclonal E-cadherin antibodies (Novocastra, NCL-E-Cad). Statistical analysis did not show any relation between the change in the location of E-cadherin expression, the patients' sex, and the location of changes. Simultaneously, we observed a strong relationship between the presence of exudate in the vessels from cancer cells, the histological grade and the loss of E-cadherin expression in the main tumour mass (p<0.01). We also noted a statistically significant correlation between the presence of lymph node invasion and distant metastases and the E-cadherin cytoplasmic reaction (p=0.0001, p=0.000001, respectively). A borderline significance of p=0.06 was noted in the association between the appearance of recurrence at the postoperative site and the change in location of E-cadherin expression in the main tumour mass from cytoplasm to membrane. On the basis of our results, we can conclude that a change in the location of E-cadherin expression (from membrane cytoplasm) is strongly associated with an increased aggressiveness of CRC, which is related to the appearance of proximal and distant metastases and to recurrence at the postoperative scar.
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PMID:Effects of changes at the site of E-cadherin expression as an indicator of colon cancer aggressiveness. 1563 79

Colorectal cancer CRC is one of the most common malignancies worldwide. Advances in molecular techniques have provided deep insight into the molecular pathogenesis, biologic and genetic changes occurring in colon cancer patients. Current theories of malignant transformation postulate that development of colon cancer is related to 2 main pathways; the loss of heterozygosity pathway, which is usually due to a defect in the adenomatous polyposis coli APC gene and microsatellite instability, which is usually due to a defect in mismatch repair MMR genes. This review summarizes the role of the wingless signaling pathway genes including APC and MMR genes in the development of CRC.
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PMID:Wingless signaling pathway family relation to colon cancer. Have we come full circle? 1575 47

HNPCC (hereditary non-polyposis colon cancer) is an autosomal-dominant disorder characterized by early-onset CRC (colorectal cancer). HNPCC is most often associated with mutations in the MMR (mismatch repair) genes hMLH1, hMSH2, hMSH6 or hPMS2. The mutator phenotype of a defective MMR system is MSI (microsatellite instability), which also occurs in approx. 15-25% of sporadic CRC cases, where it is associated with the hypermethylation of the promoter region of hMLH1. Dietary factors, including excessive alcohol consumption, ingestion of red meat and low folate intake, may increase the risk of MSI high tumour development. In contrast, aspirin may suppress MSI in MMR-deficient CRC cell lines. Butyrate, a short-chain-fatty-acid end product of carbohydrate fermentation in the colon, shares a number of anti-neoplastic properties with aspirin, including inhibiting proliferation and inducing apoptosis of CRC cells. Recent in vitro studies suggest that physiological concentrations of butyrate (0.5-2 mM) may have more potent anti-neoplastic effects in CRC cell lines deficient in MMR, but mechanisms for such a differential response remain to be established.
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PMID:DNA mismatch repair status may influence anti-neoplastic effects of butyrate. 1604 86


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