Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hereditary colonic cancer syndrome without polyposis, hereditary non-polyposis colorectal cancer (HNPCC), is usually divided into 2 main categories: hereditary site-specific colorectal cancer (Lynch syndrome I) and colorectal cancer in association with other forms of cancer (Lynch syndrome II). One problem associated with Lynch II is the uncertainty as to which types of cancer form part of the hereditary tumour spectrum. The present study was performed to obtain more information about the tumour spectrum of HNPCC. In the 24 HNPCC families studied, 104 patients had colorectal cancer (mean age at diagnosis: 46 years) and in 4 of the families this was the only type of cancer to occur. Sixty-five extra-colonic tumours were diagnosed in 20 families. Endometrial carcinoma was found in 16 patients belonging to 12 families. Cancer of the stomach occurred in 10 patients representing 5 families, and mainly in the older generations. Urinary-tract tumours were found in 8 patients from 4 families. Second primary tumours were diagnosed in 13 of the 16 patients with endometrial cancer, in 4 of the 10 patients with stomach cancer and in 7 of the 8 patients with a urinary-tract tumour. Many other types of carcinoma were found as well, but less frequently. In our families, the trait appears to be transmitted by patients with cancer of the stomach, endometrium or urinary tract, because some of their children have developed colorectal cancer. The findings suggest that, in these 24 HNPCC families, carcinomas of the endometrium, stomach and urinary tract belong to the hereditary tumour spectrum. Definite assignment of tumours to this spectrum will become possible only after a sensitive and specific biomarker becomes available. The screening programme should depend on which and how many extra-colonic tumours occur in a family.
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PMID:The tumour spectrum in hereditary non-polyposis colorectal cancer: a study of 24 kindreds in the Netherlands. 236 99

Microsatellite instability (the replication error phenotype) is a new molecular assay that identifies a substantial fraction of human cancers. The microsatellite instability in these cancers arises from alterations in the tumors of the number of mono-, di-, and trinucleotide repeats that compose the microsatellites. Microsatellite instability is typical of colon and endometrial tumors arising in members of Lynch syndrome cancer families. Microsatellite instability is also found in a substantial percentage of sporadic cases of colon, endometrial, and gastric cancer, as well as in additional sporadic cancers, such as lung cancer, not usually seen in Lynch kindreds. Thus far, four different mutant genes, all homologous to bacterial DNA repair genes, have been identified as inherited in Lynch kindreds, and therefore are associated with the replication error phenotype. Clinical implications of the replication error phenotype include the demonstration that resistance to some alkylating agents appears to be directly altered in tumors with this phenotype.
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PMID:Microsatellite instability in inherited and sporadic neoplasms. 769 68

Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) is characterized by the early onset of colorectal neoplasms, frequently localized in the right colon, increased occurrence of multiple primaries, vertical transmission and aggregation of tumours in families in accordance to a Mendelian dominant type of inheritance. The syndrome accounts for approximately 5% of all colorectal cancers. The purpose of the present study was to describe the tumour spectrum and the most relevant clinical features of 28 kindreds with HNPCC, classified according to the guidelines of the International Collaborative Study Group, and of 61 "suspected" HNPCC. These families were observed during a 6-year registration of colorectal neoplasms in a health-care district of Northern Italy. Colorectal cancer was by far the most frequent malignancy; gastric cancer was the second. Uterine carcinoma was only slightly more frequent than expected. Lung- and breast-tumour rates were lower than expected. Cancer distribution in the large bowel showed that about two fifths of the tumours developed in the right colon. The occurrence of cancer before the age of 50 to 60 was much more frequent in HNPCC. Multiple tumours developed in 25 patients with HNPCC and in 32 with "suspected" HNPCC. Pancolonoscopy remains the procedure of choice for surveillance; other examinations, such as gastroscopy, gynaecological investigations, urography and cholangiography, are suggested only to selected families. One of the main features of the study was the inclusion of 61 "suspected" HNPCC, a heterogeneous group of families which nonetheless deserves careful follow-up.
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PMID:Tumour spectrum in hereditary non-polyposis colorectal cancer (HNPCC) and in families with "suspected HNPCC". A population-based study in northern Italy. Colorectal Cancer Study Group. 850 11

Microsatellite instability (or replication error phenotyp) is a new molecular phenotyp of a substantial fraction of human cancers. The microsatellite instability in these cancers arises from alterations in normal regions of the genome consisting short sequences of repeated DNA. Ubiquitous changes in length of microsatellite sequences between constitutional and tumor DNA occur in about 90% of cases of HNPCC and in about 15% of cases of non-familial, sporadic colorectal cancer. Microsatellite instability is also found in a substantial percentage of sporadic endometrial, and gastric cancer, as well as in additional sporadic cancers, such as lung cancer which is usually not associated with HNPCC. Thus far, four different mismatch repair genes (hPMS1, hPMS2, hMLH1 hMSH2), all homologous to bacterial DNA repair genes have been identified as involved in HNPCC kindreds, and consequently they are associated with microsatellite instability. In conclusion, these basic genetic informations provide new insights into a new molecular pathway in oncogenesis, i.e. the occurrence of mutations in genomic stability genes leading to an increased cellular mutation rate (replication error phenotyp) and thus to cancer.
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PMID:[Microsatellite instability--a new aspects in genetics and molecular biology of hereditary nonpolyposis and sporadic colorectal tumors]. 908 61

Comparative genomic hybridization was used to search for DNA copy number changes in samples of gastric cancer from 12 hereditary nonpolyposis colon cancer (HNPCC) patients and in samples of sporadic gastric carcinoma from 13 patients. The gastric cancer samples from HNPCC patients showed gains affecting 19q, Xp, and whole chromosome 22, each in a single patient. Neither high-level amplifications nor losses of DNA copy number were detected. On the other hand, 10 of the 13 (77%) sporadic gastric carcinoma samples had multiple DNA copy number changes. The most frequent gains occurred with minimal common overlapping regions at 1q22-q31, 8q23-qter, 17p11.2-q22, and 20q, all at a frequency of 31%. High-level amplifications were also seen at 17q21 in three cases (23%). Losses were rare, and the most frequent loss was with a minimal common overlapping region at 4q32 (23%). This suggests that multiple DNA copy number changes are needed for the development of sporadic gastric carcinoma but not for gastric carcinoma in HNPCC patients.
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PMID:Comparative genomic hybridization reveals differences in DNA copy number changes between sporadic gastric carcinomas and gastric carcinomas from patients with hereditary nonpolyposis colorectal cancer. 977 11

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

8-oxo-deoxyguanosine triphosphate (8-oxo-dGTP) is a major oxidation product in the nucleotide pool of the cell and is a potent mutagen, because it can be incorporated into DNA with equal frequency opposite either template C or A. The human MTH1 gene (hMTH1) is a homologue of the E. coli mutator gene mutT, which encodes 8-oxo-dGTPase. hMTH1 protein reduces spontaneous mutations by removing 8-oxo-dGTP from the triphosphate pool. To determine whether this gene is associated with carcinogenesis of human ovarian cancer, the present study examined, for the first time, the hMTH1 sequence in 49 ovarian cancers and 9 ovarian cancer cell lines by means of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing analyses. A Gright curved arrow A transition at codon 83 was detected in one patient and one cell line (3.4%), followed by an amino acid change (valineright curved arrow methionine) which was known to cause the protein to be less active in vitro. This one base substitution was found in normal and corresponding tumor DNA, and its allele type was heterozygous. The same change has been detected in HNPCC (hereditary non-polyposis colorectal cancer) and gastric cancer patients, and thus it may not represent a mutation specific for ovarian cancer. A silent Tright curved arrow C transition at codon 119 was detected in 12 patients and 2 cell lines (24.1%). No specific mutations in hMTH1 were found in either ovarian cancer patients or cell lines. Thus, it appears that hMTH1 is not directly associated with ovarian cancer.
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PMID:Mutation analysis of the hMTH1 gene in sporadic human ovarian cancer. 1093 85

1-5% of all patients presenting with colorectal cancer, have an underlying genetic predisposition with an autosomal dominant of pattern of inheritance. Recently the underlying molecular genetic pathway of this syndrome known as HNPCC (hereditary nonpolyposis colorectal cancer) has been characterized: the predisposition is due to a pathogenic mutation in one of the DNA mismatch-repair genes. Colorectal cancers are the leading characterisitic of the syndrom and are frequently encountered at a young age of onset. However, endometrial cancer, stomach cancer, small bowel cancer, urinary tract cancer and skin cancer among others are also inherent to the syndrome. Based on the identification of the underlying molecular genetic pathway, predictive testing has become an option. Once the family-specific underlying pathogenic mutation in one of the DNA mismatch-repair genes has been identified in a proband, at-risk family members may be offered DNA testing with an unequivocal answer to if or if not they have inherited the increased cancer susceptibility. Multiple facets of family DNA testing require a multidisciplinary approach integrating clinicians, geneticists, psychologists, molecular biologist and pathologists. Mutations are identified in a rate of 50-60% of families complying with the Amsterdam criteria for HNPCC. The incidence of recta cancer in HNPCC has as yet not clearly been defined, due to a lack of unequivocal data. In a retrospective analysis (submitted) rectal cancers were encountered in 30% of the HNPCC patients. Half of the patients affected developed metachronous colon cancers. It is essential to address the issue of prophylactic surgery in HNPCC patients presenting with colorectal cancer: Prospective data is required in order to decide which of the options is more beneficial for the HNPCC patient presenting with his first colorectal primary: subtotal colectomy and ileorectal anastomosis versus restorative proctocolectomy. It is evident that apart from the more clinical data quality of life data must be evaluated in this study.
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PMID:[Hereditary nonpolyposis colorectal carcinoma (HNPCC): surgical aspects]. 1132 7

Hereditary nonpolyposis colon cancer (HNPCC), also known as Lynch syndrome, is characterized by germline and somatic mutations of DNA mismatch repair genes with dominant inheritance of site-specific colorectal cancer or colorectal cancer plus cancers of extracolonic sites. We describe two Taiwanese HNPCC families with members who had predominantly gynecologic malignancies. In one family, the 53-year-old proband was found to have five synchronous and metachronous tumors of the genitourinary system, which included endometrial adenocarcinoma, cervical squamous cell carcinoma, ureteral and bladder transitional cell carcinoma, and ovarian teratoma. Fourteen of her first- and second-degree relatives were victims of genitourinary and gastrointestinal malignancies. The other family was characterized by four sisters who developed endometrial adenocarcinomas at young ages (36-42 yr). Their father died of both stomach cancer and colon cancer at age 47. The diagnosis of HNPCC was confirmed in this family by genetic analysis. A heterozygous germline mutation (G5 to G6 frame-shift at 183-187) of the hMSH2 (human MutS homolog 2) gene was identified in white blood cells of all the affected family members. The frequent presentation of genitourinary cancers in HNPCC highlights the importance of family-history taking in patients with gynecologic cancers and a genetic diagnosis of HNPCC.
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PMID:Hereditary nonpolyposis colorectal cancer with gynecologic malignancies: report of two families in Taiwan. 1139 27

The molecular basis for most non-HNPCC familial colorectal cancer cases is unknown, but there is increasing evidence that common genetic variants may play a role. We investigated the contribution of polymorphisms in two genes implicated in the pathogenesis of colorectal cancer, cyclin D1 (CCND1) and E-cadherin (CDH1), to familial and sporadic forms of the disease. The CCND1 870A/G polymorphism is thought to affect the expression of CCND1 through mRNA splicing and has been reported to modify the penetrance of HNPCC. Inactivation of E-cadherin is common in colorectal cancer, and truncating germline mutations have been reported to confer susceptibility to colorectal as well as diffuse gastric cancer. The -160A/C CDH1 polymorphism appears to affect expression of CDH1 and may therefore also confer an increased risk. We found a significantly higher frequency of CCND1 870A allele in 206 familial cases compared to 171 controls (P=0.03). Odds ratios in heterozygotes and homozygotes were 1.7 (95% CI: 1.0-2.66) and 1.8 (95% CI: 1.0-3.3) respectively. The difference was accounted for by an over-representation of A allele in non-HNPCC familial cases (P=0.007). Over-representation of the CCND1 A allele was also seen in sporadic colorectal cancer cases compared to controls but this did not attain statistical significance (P=0.08). No significant differences between the frequency of CDH1 -160A/C genotypes in familial, sporadic colorectal cancer cases and controls were seen, although a possible association between the low expressing A allele and right-sided tumours was detected in familial cases.
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PMID:Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. 1189 26


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