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

The entire nucleotide sequence of the genome must be transmitted from one generation to the next with no or few errors. Preservation of this integrity requires multiple genes whose alteration can lead to an early event in tumorigenesis by increasing the mutation rate. This mutator phenotype would provide a continuing pool of mutants upon which selection could act to promote a tumor. Recent evidence consistant with this hypothesis is the mutator phenotype of tumor cells of patients with a hereditary form of colon cancer (HNPCC) which exhibit a several hundred-fold increase in spontaneous mutations in addition to a high degree of microsatellite instability. The multiple genomic alterations increasingly reported as associated with most cancers may therefore be linked to a variety of DNA metabolic processes guardians of the genome, including fidelity of the DNA synthesis and mismatch repair. The connection between cancer and deregulation of nucleotide synthesis, imbalance of the pools of nucleotides, deficiency of DNA polymerases, and mismatch repair is the subject of this review. We consider how perturbation in these DNA transactions results in instability of the genome and cancer.
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PMID:DNA synthesis, mismatch repair and cancer. 945 65

The true incidence of rectal cancer in HNPCC is still unknown. In our retrospective series analyzing 42 probands from HNPCC families, we found rectal cancer primaries in 29% of our probands. Patients with a first cancer diagnosed in the rectum developed metachronous colon cancer in 54% of the cases. These numbers indicate a requirement to discuss the most appropriate surgical procedure for preventive intervention (ileorectal anastomosis versus ileoanal pouch procedure).
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PMID:[Rectal carcinomas in HNPCC]. 993 14

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

The authors report a case of non-polyposis colon cancer in a seventeen year old female without prior polyposis or family history. Since it was the first case in this family, HNPCC was suspected. The polymerase chain reaction (PCR) of the tumor revealed changes in four polymorphic regions. Analysis of two of them, indicated the loss of genetic material confirming instability suggestive of HNPCC. The patient underwent ileorectal anastomosis and adjuvant chemotherapy with a good outcome. The authors discuss the importance of family history, genetic and immunohistochemistry studies, and the instability of microsatellites in adolescents with colorectal cancer.
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PMID:Genetics and colorectal cancer (HNPCC) in adolescence. A case report. 1043 36

A patient who had triple cancer (colon cancer, endometrial cancer, and ovarian cancer) in HNPCC kindred is reported. Her family history revealed the occurrence of colon cancer in her paternal aunt and in two cousins, fulfilling the minimum HNPCC criteria. Microsatellite instability analysis revealed replication error (RER)+ in all cancer lesions at 2 microsatellite loci (D1S191, BAT 40). SSCP analysis suggested germline mutation in exon 2 of the hMSH2 gene. This case showed the importance of complete family-history investigations to identify HNPCC patients. In the near future, definitive diagnosis of HNPCC will be possible on the basis of DNA studies.
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PMID:Microsatellite instability and hMSH2 gene mutation in a triple cancer (colon cancer, endometrial cancer, ovarian cancer) patient in hereditary non-polyposis colorectal cancer (HNPCC) kindred. 1068 Mar 34

Familial risk of colon cancer is a commonly encountered issue, involving both rare inherited syndromes of colon cancer and common familial clustering of cases. The genes that give rise to the rare syndromes of FAP and HNPCC are now known and current research is addressing the cellular mechanisms of these genes and the proper application of genetic testing in families with one of the syndromes. Common familial clustering of cases appears to arise from an interaction of mildly to moderately severe inherited susceptibility factors with certain environmental factors to give rise to adenomatous polyps and then finally colorectal cancer. Research in this area involves identification of these purportedly more common susceptibility genes, and determination of how each interacts with environmental factors to give rise to polyps and cancer. Optimal application of varying degrees of familial risk to screening strategies is also being determined.
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PMID:Familial association. 1070 79

Deficiencies in DNA mismatch repair (MMR) have been found in hereditary colon cancers (hereditary non-polyposis colon cancer, HNPCC) as well as in sporadic cancers, illustrating the importance of MMR in maintaining genomic integrity. We have examined the interactions of specific mismatch repair proteins in human nuclear extracts. Western blot and co-immunoprecipitation studies indicate two complexes as follows: one consisting of hMSH2, hMSH6, hMLH1, and hPMS2 and the other consisting of hMSH2, hMSH6, hMLH1, and hPMS1. These interactions occur without the addition of ATP. Furthermore, the protein complexes specifically bind to mismatched DNA and not to a similar homoduplex oligonucleotide. The protein complex-DNA interactions occur primarily through hMSH6, although hMSH2 can also become cross-linked to the mismatched substrate when not participating in the MMR protein complex. In the presence of ATP the binding of hMSH6 to mismatched DNA is decreased. In addition, hMLH1, hPMS2, and hPMS1 no longer interact with each other or with the hMutSalpha complex (hMSH2 and hMSH6). However, the ability of hMLH1 to co-immunoprecipitate mismatched DNA increases in the presence of ATP. This interaction is dependent on the presence of the mismatch and does not appear to involve a direct binding of hMLH1 to the DNA.
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PMID:Identification of mismatch repair protein complexes in HeLa nuclear extracts and their interaction with heteroduplex DNA. 1074 59

The APC I1307K gene mutation is associated with increased colorectal cancer (CRC) risk in Ashkenazi Jews. Factors predicting acceptance of this and other hereditary colon cancer mutation tests in a clinical setting are unknown. We analyzed sex, age, family history, personal history, and gene test results of patients at increased risk for cancer who sought cancer risk counseling at the Johns Hopkins (JH) CRC Risk Assessment Clinic (n = 91), and those submitting samples to the JH Pathology Molecular Diagnostic Laboratory (n = 256) for APC I1307K testing. Of patients seen at the JH Clinic, 77/91 (84.6%) elected APC I1307K testing after pretest counseling (acceptors). There were no statistically significant differences in demographic characteristics between acceptors and decliners. In comparison, only 8 of 57 (14.0%) patients offered HNPCC testing proceeded with testing (P < 0.001). Of 256 individuals tested at the JH laboratory, most were male (61.3%) and most had a personal or family history of colorectal cancer or polyps. Test positivity correlated with increasing risk of colorectal cancer. Acceptance of testing for the APC I1307K mutation is high, with more men than women pursuing counseling and testing. The reported association between the APC I1307K mutation and colon cancer risk was supported by a correlation in these data between personal or family history of CRC or polyps and a gene mutation.
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PMID:Response to genetic counseling and testing for the APC I1307K mutation. 1075 45

In the field of mass detection of colorectal cancer by Hemoccul test, the results of the Burgundy study confirm the two european studies previously published and encourage to extend this training to the whole country. In oncogenetic field, a recent publication suggest some different clinical criteria that Amsterdam criteria to define a Lynch syndrome. When genetic markers are performed in a population selected according to these type I criteria, HNPCC mutation could be detected in 28% of cases. In colorectal cancer surgery, the debate remains open on the place of coeliosurgery. A recent published series of 135 colon cancers operated by coeliosurgery do not show any recurrence on trocar orifices. A US study has confirmed the prognostic value of the number of lymph nodes analyzed after resection of colorectal cancer. In adjuvant treatment of stage II colon cancer, two contradictory publications have been reported in the Journal of Clinical Oncology. However, the results of the Impact B2 Group are more consistent and support the fact that chemotherapy cannot be recommended as a standard treatment in state II colon cancer. The actualities in the liver metastases focused on the new local destruction technics that are cryosurgery and radiofrequency. Concerning the chemotherapy of metastatic colorectal cancer, important results have been published in second line therapy showing the superiority of Campto compared to best supportive care or 5FU based chemotherapy both in term of overall survival and quality of life. In first line chemotherapy, the superiority of bi-therapies (LV5FU2 and oxaliplatin or LV5FU2 and irinotecan) has been confirmed compared to LV5FU2 alone. A recent publication showed that patients older than 70 years tolerate chemotherapy for colorectal cancer as well as younger patients with the same efficacy. In esophagus carcinoma, the most important study didn't show any efficacy of neoadjuvant chemotherapy by 5FU-cisplatin in operable adenocarcinoma of squamous carcinoma of esophagus. The final results of dutch's study in node dissection for gastric cancer do not find any benefit in overall survival comparing D2 versus D1 dissection with a substantial increase in morbidity and mortality in the D2 arm, specially when splenopancreatectomy was performed. Finally, an important study has confirmed the value of per echoendoscopy biopsies for the diagnosis of positive lymph nodes and pancreatic tumors.
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PMID:[Update on gastroenterology]. 1090 87

Hereditary nonpolyposis colorectal cancer (NHPCC) is the most common form of inherited colon cancer and one of the most frequent autosomal dominant disorders. HNPCC presents an early onset of colorectal cancer (< 50 years), proximal localization of the colonic tumors, and high risk of developing multiple primary colorectal tumors as well as extracolonic tumors. This disease is caused by mutations in at least four DNA mismatch repair genes, (hMSH2, hMLH1, hPMS1 and hPMS2) and estimations indicate that it affects 1:200-1:2,000 people in the Western populations. The identification of the genes responsible for HNPCC has prompted the search for mutations in affected individuals. DNA from an affected member of a family was sent to a Dutch HNPCC Diagnosis Centre. This Centre reported a germinal mutation, which introduces a premature stopcodon and causes the production of a truncated protein. This particular mutation has not been previously registered in the database of mutations related to this disease. After the identification of the mutation in the index patient, we have developed a quick and efficient procedure for detecting mutations in the rest of the family. The methodology is based on the amplification of the exon 13 in the hMSH2 gene using a forward primer that abuts the mutation site and introduces the cutting sequence of the enzyme Haelll++ only in the wild type allele. At present, seventeen members of the family have been diagnosed and nine have been found to be affected. The methodology is simple, specific, sensitive, inexpensive and applicable in low complexity laboratories.
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PMID:[Diagnosis by directed mutagenesis of a mutation at the hMSH2 gene associated with hereditary nonpolyposis colorectal cancer]. 1096 7


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