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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

Colo-rectal cancer in young patients is a subject of interest for many reasons. Various studies are devoted to this subject but controversies regarding the stages, the evolution and the prognosis still remains. We present intermediate results, of an ongoing study, which is directed to those particular aspects of colon cancer of the patients less than 45 years of age in a region where the global incidence of the disease is one of the highest in the world. In the past five years, we have observed 602 patients with colon cancer. 23 of them (4%) were less than 45 years old. The age at diagnosis was 38 +/- 6 years. Two-thirds of the subjects were male. 13% had had predisposing conditions for colon cancer such as FAP, ulcerative colitis or Turcot syndrome; 50% had a positive familial history for cancer. Symptoms lasted for less than 3 months in two thirds of the patients. 15% had a right sided tumor, 38% were located in the sigmoid and 28.5% in the rectum. At diagnosis, the tumors were classified as follows: 32% Dukes B, 23% Dukes C and 40% were disseminated disease. Most of them were located in the rectum, but 43% of Dukes B lesions were located in ascending or transverse colon. Grading reveal moderately to poorly differentiated tumors in 3/4 of cases. 30% of patients received an adjuvant therapy. After two years, 70% of the patients were alive. None of them with Dukes A or B but one of the patients with Dukes C were dead.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Colorectal cancer before 45 years of age]. 164 6

Molecular genetic studies of tumor-specific allele loss, originally associated primarily with research regarding childhood hereditary cancers such as retinoblastoma and Wilms' tumors, only lately have been recognized as a relatively fast and fruitful way of locating cancer genes on human chromosomes. To date, over 25 different cancers have been tied to a gene (or genes) on a specific chromosome when this method has been used. During the past year alone, this approach has permitted detection of three genes involved in either hereditary or sporadic colorectal cancers. These three genes, located on chromosomes 5q, 17p, and 18q, are believed to belong to the newly described tumor suppressor (or growth suppressor) gene class, whose effects are opposite those of activated cellular oncogenes, which promote uncontrolled cell growth. Present studies, however, have not shown losses of any of these tumor suppressor genes to be correlated with the presence of activated ras genes in colorectal adenomas or carcinomas. During progression from adenoma to carcinoma, ras gene mutations and 5q allelic deletions are likely to be earlier events, whereas allelic losses from chromosomes 18q and 17p seem to occur more often in advanced tumors. Involvement of the genes on 5q (FAP) and 18q (Lynch syndrome II) in hereditary colon cancer syndromes is supported by linkage studies, but their respective roles (as well as that of the gene on 17p) in familial and sporadic colorectal cancer remain to be precisely defined. Probable isolation of these three genes by molecular cloning within the next few years will help elucidate their specific biologic functions. It will also permit early detection, and thus prevention, of some familial colon cancers (such as FAP), and possibly allow DNA marker-based separation of different colon cancer subtypes of similar histologic appearance.
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PMID:Molecular genetic studies of colon cancer. 264 66

Colorectal cancer is the second most common cancer in the United Kingdom and other developed countries in the West. Although it is usually not familial, there is a rare dominantly inherited susceptibility to colon cancer, familial adenomatous polyposis (FAP; also often previously called familial polyposis coli). During adolescence affected individuals develop from a few hundred to over a thousand adenomatous polyps in their large bowel. These are sufficiently likely to give rise to adenocarcinomas to make prophylactic removal of the colon usual in diagnosed FAP individuals. Adenomas may occur elsewhere in the gastrointestinal tract and the condition is often associated with other extracolonic lesions, such as epidermoid cysts, jaw osteomata and fibrous desmoid tumours. Adenomata have been suggested to be precancerous states for most colorectal tumours. Knudson has suggested that the mutation for a dominantly inherited cancer susceptibility may be the first step in a recessive change in the tumour cells, and that the same gene may be involved in both familial and non-familial cases of a given tumour. Following up a case report of an interstitial deletion of chromosome 5 in a mentally retarded individual with multiple developmental abnormalities and FAP, we have now shown that the FAP gene is on chromosome 5, most probably near bands 5q21-q22.
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PMID:Localization of the gene for familial adenomatous polyposis on chromosome 5. 303 73

The chemotherapy of gastric carcinoma is at an important point in its evolution. Multiple studies with a variety of agents have demonstrated that combination chemotherapy appears to be superior to single-agent chemotherapy in regard to response rate but not survival rate. The typical single agent results in response rates of 20% or less, whereas the typical combination chemotherapy regimen results in response rates of 30% to 50%. The FAM (5-fluorouracil [5-FU], doxorubicin, mitomycin C) chemotherapy regimen, widely used during the last 10 years, produces partial responses (PRs) in 35% of patients. However, the overall complete response (CR) rate is only 2%. Long-term survival of patients with disseminated malignancy is only achieved when treatments produce CR of disease. Because available combination chemotherapy approaches to gastric cancer only produce PRs, it is not surprising that there has been no impact on patient survival from these approaches. There are several newer approaches that hold promise in the treatment of gastric cancer. For example, the role of cisplatin in gastric cancer has not been completely defined. A recent study of FAP (5-FU, doxorubicin, cisplatin) has reported a 50% response rate with a significant number of CRs. The FAP regimen needs further exploration. The drug triazinate appears to have activity in gastric cancer, and in combination with mitomycin C produces a 28% response rate in patients who had failed chemotherapy regimens containing fluorinated pyrimidine. Thus, the efficacy of this drug needs further exploration in stomach cancer therapy. There is no clear definition of the future role of hepatic arterial infusion in gastric cancer. There is no question that, in colon cancer, response rates with fluorinated pyrimidine alone or fluorinated pyrimidine with mitomycin C are in the range of 50% when hepatic arterial infusion is used. This approach needs to be explored in gastric cancer. Finally, the use of intraperitoneal (IP) therapy in patients with minimal disease should be explored, because a common form of relapse in carcinoma of the stomach is IP dissemination.
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PMID:Chemotherapy of advanced gastric cancer: present status, future prospects. 329 18

This is the first report of chromosome 18 allele loss in colorectal carcinomas from FAP patients and concurrent allele losses on chromosomes 5 and 18 in sporadic colorectal cancer. This is based on our investigation of twenty-two colorectal carcinomas from sporadic cases and FAP patients which revealed tumor-specific allele loss of at least 44% at the D18S6 locus on chromosome 18 in informative cases. These results coupled with the tentative assignment of an HNPCC gene to chromosome 18 suggests that a gene on chromosome 18 may be involved in the etiology of some colon cancers. Possible mechanisms involving genetic changes on chromosome 18 in colon cancer are discussed in relation to tumor- or growth-suppressor genes.
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PMID:Chromosome 18 allele loss at the D18S6 locus in human colorectal carcinomas. 341 2

The lectin GS I-A4 binds to terminal alpha-N-acetylgalactosaminyl (GalNAc) groups (which include the Tn antigen), but not to the closely related tumor-associated epitope, sialylated Tn antigen. The lectin also precipitates asialo OSM, but not its native sialylated form. Lectin histochemistry with human colonic tissues showed that GS I-A4 specifically stained specimens of colon cancer and colonic tissues from individuals with FAP; however, normal colonic tissues from patients without colonic disease were rarely stained with this lectin. Glycoconjugates bound by GS I-A4 were observed on the surface membranes of 2 human colon cancer cell lines, LS174t and SW1116, when fluorescein isothiocyanate (FITC)-conjugated GS I-A4 was used. GS I-A4 was toxic to these 2 human colon cancer cell lines in monolayer culture. A dose-response study conducted using 10-160 micrograms/ml, of GS I-A4 demonstrated significant dose-related toxicity against LS174t and SW1116 cells. At concentrations > 80 micrograms/ml, > 99% of LS174t and > 90% of SW1116 cells were killed. Four mM GalNAc specifically inhibited the cytotoxic effect of GS I-A4 (p < 0.001), whereas 4mM N-acetylglucosamine (GlcNAc) had no effect. Two other lectins that recognize terminal alpha-GalNAc residues, DBA and LBL, were significantly less cytotoxic to the colon cancer cells than GS I-A4. In the light of these findings, we speculate that GS I-A4 may have potential use as a diagnostic agent against colorectal cancer.
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PMID:The lectin Griffonia simplicifolia I-A4 (GS I-A4) specifically recognizes terminal alpha-linked N-acetylgalactosaminyl groups and is cytotoxic to the human colon cancer cell lines LS174t and SW1116. 751 54

Familial risk of colon cancer is common. The rare syndromes of FAP and HNPCC account for a small fraction of familial cases. A working knowledge of these syndromes is important, however, because appropriate management can prevent most cases of colon cancer in families with these conditions. Furthermore, the genes that give rise to FAP and HNPCC have been identified, and genetic testing to find gene carriers in affected families is now commercially available. In addition to the syndromes, colon cancer commonly clusters in families. The risk of colon cancer is two to threefold increased when a first-degree relative is affected with this malignancy. The risk is further increased if multiple first-degree relatives have colon cancer or if a diagnosis in a relative is made at an age of 50 years or younger. The genetic causes of this more commonly observed of familial clustering have not been clarified, but screening based on the degree of familial risk has been suggested.
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PMID:Familial risk and colorectal cancer. 896 Aug 93

The accumulating evidence suggests that aspirin or other NSAIDs may prevent or inhibit the development of colon and perhaps other digestive tract cancers. Although the clinical, experimental, and epidemiologic evidence is promising, the hypothesis remains unproven except in the models of chemically induced colon cancer in rodents and adenomatous polyps in patients with FAP. Clinicians should await the results of randomized trials before using NSAIDs for cancer prevention or treatment. Recommendations are as follows: 1. Experimental studies should define the mechanism or mechanisms by which NSAIDs inhibit tumorigenesis in the rodent model. 2. Experimental and clinical studies should define the optimal drug, dosage, and treatment regimen. The new, selective COX-2 inhibitors should be studied for efficacy and toxicity. 3. Epidemiologic studies should continue to explore the issues of dosage, duration, drug, and toxicity. Because full-scale, randomized trials are feasible only for studying intermediate end points such as polyp recurrence or proliferative indices in high-risk populations, epidemiologic studies have an ongoing role. 4. Carefully designed randomized, clinical trials, now underway, are needed to test the efficacy of NSAIDs in inhibiting colorectal polyps or cancer in humans. 5. Better criteria are needed as to who should take aspirin and who should not.
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PMID:NSAID use and decreased risk of gastrointestinal cancers. 922 76

The large bowel is a leading site for cancers in developed countries whereas small bowel cancers are rare worldwide. The incidence rates of both large and small bowel cancer are low in India, and rectal cancer is more common than colon cancer. The incidence rates of colon cancer in eight population registries vary from 3.7 to 0.7/100,000 among men and 3 to 0.4/100,000 among women. For rectal cancer the incidence rates range from 5.5 to 1.6/100,000 among men and 2.8 to 0/100,000 among women. One intriguing observation is the occurrence of rectal cancer in young Indians. Rural incidence rates for large bowel cancers in India are approximately half of urban rates. Based on data from eight registries, we estimate that, in the year 2001, the incidence of large bowel cancer in India will be 18,427 in men and 13,092 in women. Immigrant studies reveal an increase in incidence as compared to the rates in native counterparts. Reliable time trends for India are available only from the Bombay registry. Significant increase in the incidence of colon cancer has been reported for both men and women over two decades, but the rates of rectal cancer are steady. The low incidence of large bowel cancers in Indians can be attributed to high intake of starch and the presence of natural antioxidants such as curcumin in Indian cooking. The role of hereditary factors has been evaluated in a few studies. Some studies have reported the occurrence of both FAP and HNPCC in India. There are no Indian studies on large bowel cancer prevention. The prevalence of adenomas is rare in elderly Indians undergoing colonoscopy, even in those with large bowel cancers. Small bowel cancers are extremely rare in India and no analytical studies have been published. Hospital-based data suggest that lymphomas of small bowel are more common than carcinomas. In conclusion, the incidence of large and small bowel adenomas and cancers is low in Indians. Increase in the incidence of large bowel cancers in immigrants and urban Indians compared to rural populations supports a role for environmental risk factors including diet. High rates of rectal cancers in young Indians could suggest a different etiopathogenesis, which is neither inherited nor traditional diet-related.
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PMID:Epidemiology of digestive tract cancers in India. V. Large and small bowel. 1040 66


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