PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “COLORECTAL CANCER GENES”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed2004

No association between the Arg201Gly polymorphism of the DCC gene and colorectal cancer.

BACKGROUND AND AIMS: In one small study, the DCC Arg201Gly polymorphism has been observed more frequently in colorectal cancer cases compared with controls. We wondered whether these results could be replicated in a much larger study. METHODOLOGY: The DCC Arg201 Gly polymorphism was genotyped in 625 unselected Caucasian colorectal cancer patients and 220 controls. Association analysis was used to search for a difference between patients and controls. Subgroup analyses were performed for site of tumour, gender, age at diagnosis, family history of colorectal cancer and modified Dukes classification. RESULTS: The association analyses revealed no difference in Arg201Gly genotype frequency between patients and controls, neither overall nor for different subgroups according to site of tumour, gender, age at diagnosis, family history of colorectal cancer and modified Dukes classification. CONCLUSION: No association was observed between the Arg201Gly polymorphism of DCC and colorectal cancer risk.

Adult↗
PubMed1993

Heritable colorectal cancer and cancer genes: systemic expressions.

Epidemiological studies of heritable cancer have demonstrated that cancer predisposition is a dominant trait; these studies have also predicted the recessive outcome of the neoplastic process. Biochemical studies of dominantly heritable cancer have demonstrated the relevance of systemic effects. The systemic effects are presumably due to a dominant mutation at the "initiator locus." Collectively they define cancer initiation at the cellular level (as described in this review). Molecular biological studies have demonstrated that cancer progression and the appearance of clinical cancer occur through an accumulation of recessive mutations at critical loci. We must continue to try to define not only the inherited and acquired gene defects that initiate the neoplastic state but also the subsequent genetic alterations and biomarkers involved in tumor progression. These genetic defects are already proving useful in diagnosis and prognostication. The hope is that these biomarkers may be useful for designing specific differentiation therapy.

Colorectal Neoplasms↗
PubMed2006

Prospective results of surveillance colonoscopy in dominant familial colorectal cancer with and without Lynch syndrome.

BACKGROUND & AIMS: Lynch syndrome is an autosomal dominant predisposition to colorectal cancer caused by mutations in DNA mismatch repair genes; colorectal cancer risk is high. Few studies have addressed colorectal cancer risk in individuals from dominant families without mismatch repair deficiency. We sought to establish whether these individuals are also at increased risk by examining the incidence of advanced neoplasia during surveillance. METHODS: In this prospective cohort study, BAT26 testing of tumors was carried out at 2 tertiary centers on 125 individuals from 97 families (with a dominant colorectal cancer history) to classify families as Lynch syndrome (microsatellite unstable) or non-Lynch syndrome (microsatellite stable). Colonoscopy results in 288 at-risk family members were compared. RESULTS: Twenty-nine families were classified as Lynch syndrome and 68 as non-Lynch syndrome. Seven hundred seventy-six colonoscopies were undertaken. High-risk adenomas occurred in 7 of 91 (7.7%) Lynch syndrome individuals and 15 of 197 (7.6%) non-Lynch syndrome individuals, adjusted relative risk 1.15 (95% CI: 0.6-2.3). Cancer was observed only in Lynch syndrome individuals (4/91; 4.4%), Fisher exact test, P = .010. Multiple adenomas were only seen in non-Lynch syndrome individuals (13/197; 6.6%), Fisher exact text, P = .06. CONCLUSIONS: Individuals with an autosomal dominant family history of colorectal cancer with and without evidence of Lynch syndrome are at equal risk of high-risk adenomas during surveillance, but colorectal cancer was only seen in Lynch syndrome. Therefore non-Lynch syndrome individuals do require colonoscopic surveillance, but the interval could be lengthened because risk of (interval) cancer is low. Lynch syndrome individuals require short surveillance intervals as is the recommended practice.

Age Distribution↗
PubMed1998

Differential effects of sodium butyrate on the transcription of the human TIS11 family of early-response genes in colorectal cancer cells.

The tetradecanoyl phorbol acetate (TPA)-inducible sequence 11 (TIS11) family of early-response proteins consists of at least five members. They share a highly conserved Cys3His zinc-binding motif, but otherwise have little sequence similarity. Their function remains unknown, but all are induced rapidly and transiently in response to extracellular hormone and growth factor signals. Sodium butyrate, a fermentation product of dietary fibre, effects colorectal cancer cell proliferation by inducing growth arrest, differentiation and apoptosis. In this communication, we report that butyrate has differential effects on the transcription of the three human TIS11 family members identified so far in T84 and HT-29 human colorectal cancer cell lines. Butyrate response factor 1 (BRF1) transcription is repressed, butyrate response factor 2 (BRF2) transcription is activated and there is no apparent effect on the transcription of human TIS11 (HTIS11). Induction and repression occur rapidly, with altered mRNA levels detectable within 15 min of butyrate addition. Two other short-chain fatty acids, propionate and acetate, have no detectable effects on BRF1 or BRF2 transcription.

Butyrate Response Factor 1↗
PubMedDate not supplied

Tumor-specific chemo-radio-gene therapy for colorectal cancer cells using adenovirus vector expressing the cytosine deaminase gene.

We studied the effect of suicide gene therapy using an adenovirus vector expressing the cytosine deaminase (CD) gene combined with irradiation therapy (chemo-radio-gene therapy) for human colorectal cancer cells. Since serum CEA levels are elevated in patients with some malignant tumors including colorectal cancer, we applied the CEA promoter to chemo-radio-gene therapy, expecting tumor-specific expression of the CD gene. In in vitro study, we succeeded in selective expression of the target CD gene and growth inhibition in only CEA-producing tumor cells; Further the inhibitory effect was enhanced by combination with radiation therapy in an irradiation dose-dependent manner. In addition, in in vivo study, a significant growth inhibition was observed in chemo-radio-gene therapy in comparison with radiation therapy alone or suicide gene therapy alone. Thus, we suggest that tumor-specific chemo-radio-gene therapy may be a useful strategy for human colorectal cancer.

Adenocarcinoma↗
PubMed2003

Prognostic significance of the allelic loss of the BRCA1 gene in colorectal cancer.

BACKGROUND: Survival at the intermediate stage of colorectal cancer (CRC) is less predictable than in the early and advanced stages. Several genetic markers possibly involved in growth and progression of CRC can be used for prognosis. AIMS: This study investigated the proportion of allelic loss (loss of heterozygosity (LOH)) at the BRCA1 locus in sporadic CRC and its value in patient prognosis. PATIENTS AND METHODS: A total of 314 patients were investigated for LOH at the BRCA1 locus using polymerase chain reaction by means of three intragenic polymorphic microsatellite markers. Allelic losses were compared with clinicopathological characteristics of patients, recurrence rate, disease free survival (DFS), and overall survival. RESULTS: Twenty six patients were excluded because of microsatellite instability. Of the remaining 288 cases, 244 (84.7%) were informative, with 97 (39.8%) patients bearing BRCA1 LOH. Recurrence rate was higher in patients with LOH (p=0.0003), and DFS was 73.3% (SEM 5.7) at five years in patients without LOH, and 49.2% (7.1) in cases with positive allelic loss (p=0.0004). Retention of alleles at the BRCA1 locus was associated with a favourable DFS in stages I and II (p<0.05). The presence of LOH was also significantly associated with short overall survival (p=0.02). Multivariate analysis in the complete series showed that stage (p=0.006) and lymph node metastases (> or =4 nodes, p=0.0001; 1-3 nodes, p=0.038) were independent prognostic factors. However, multivariate study by stages revealed that BRCA1 LOH was an independent prognostic factor in stages I and II (p=0.001). CONCLUSIONS: BRCA1 LOH is a molecular alteration present in CRC, with unfavourable repercussions for overall survival, that could be considered as an outstanding independent prognostic factor in stages I and II.

Aged↗
PubMedDate not supplied

Methylenetetrahydrofolate reductase C677T is not associated with expression of pyrimidine metabolic enzyme genes in colorectal cancer.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may influence the chemosensitivity of colorectal cancers to fluorouracil (5-FU) by increasing intracellular 5,10-methylenetetrahydrofolate. The effect of this polymorphism on the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase (TP) in colorectal cancer was investigated. The MTHFR C677T polymorphism was analysed and TS, DPD, OPRT and TP mRNA expression was measured in tumour and adjacent normal mucosal tissue. In all patients, the genotypes of the tumour and normal tissues were identical. No differences were found in the expression of TS, DPD or TP mRNA by genotype in either tumour or normal tissue. Although the OPRT mRNA level in tumour tissue was not associated with the genotype, normal mucosa with the TT genotype showed a significantly higher OPRT mRNA level than mucosa with other genotypes. The MTHFR C667T polymorphism is not associated with intratumoural expression of TS, DPD, OPRT or TP.

Aged↗
PubMed2001

The methylenetetrahydrofolate reductase (MTHFR) gene in colorectal cancer: role in tumor development and significance of allelic loss in tumor progression.

BACKGROUND AND AIM: Folate deficiency predisposes to sporadic colorectal cancer (CRC). Methylenetetrahydrofolate reductase (MTHFR) is a critical folate-metabolising enzyme and a polymorphism at position 677 (C677T), is associated with reduced enzyme activity. We investigated whether this functional polymorphism modulates the risk of developing CRC. METHODS: This was a retrospective case-control study. 136 unselected cases of sporadic CRC and 848 normal population controls were genotyped for the MTHFR C677T polymorphism. Tumor tissue was genotyped to assess loss of heterozygosity (LOH). RESULTS: MTHFR CT heterozygotes had a significantly increased risk of developing CRC (53.7% of CRC cases vs 38.4% of controls), odds ratio 1.86 (95% CI 1.3-2.7, p < 0.005). No increased cancer risk was observed in TT homozygotes. The MTHFR 'T' allele frequency was significantly higher in the cancer group (0.3713) as compared to controls (0.2900, p < 0.008). LOH at the MTHFR locus was observed in 18% of informative cancers, with exclusive loss of the variant 'T' allele, in all cases. CONCLUSION: In this study of a homogenous northern European population, MTHFR CT heterozygotes had an almost two-fold increased risk of developing sporadic CRC. The exclusive pattern of MTHFR allele loss in cases of LOH, suggest that functional MTHFR activity within a tumor might play an important role in the survival and progression of a colonic neoplasm.

Adenocarcinoma↗
PubMed2001

Mutations in the carcinoembryonic antigen gene in colorectal cancer patients: implications on liver metastasis.

Carcinoembryonic antigen (CEA) expression is used clinically to monitor patients with colorectal and other cancers. A subset of patients have extraordinarily high CEA levels that cannot be attributed solely to tumor load. We have shown mutations in the region of CEA (PELPK motif) responsible for its hepatic clearance in three of eight patients with high CEA levels. We used denaturing high-performance liquid chromatography to provide evidence of polymorphism in these patients. These mutations were scored by DNA cycle sequencing and shown to be heterozygous. The patients with mutations in the PELPK motif showed remarkably reduced circulatory clearance rates in an animal model. A patient without mutation in the region showed normal clearance rates. Mutations in PELPK may affect structural stability and binding affinity to the Kupffer cell receptor in the liver. These studies have implications for the role of CEA as a facilitator of hepatic metastasis.

Amino Acid Sequence↗
PubMed1995

Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer.

The TGF beta type II receptor (RII) was found to be mutated within a polyadenine tract in 100 of 111 (90%) colorectal cancers with microsatellite instability. Other polyadenine tracts of similar length were mutated in these samples but not as frequently as RII. In most cases, the polyadenine tract mutations affected both alleles of RII, and in four tumors heterozygous for the polyadenine mutations, three had additional mutations that were expected to inactivate the other RII allele. These genetic data support the idea that RII behaves like a tumor suppressor during CR cancer development and is a critical target of inactivation in mismatch repair-deficient tumors.

Animals↗
PubMed1998

Selective expression of carcinoembryonic antigen promoter in cancer cell lines: targeting strategy for gene therapy in colorectal cancer.

PURPOSE: This study was designed to characterize the mechanisms regulating the expression of the human carcinoembryonic antigen promoter (pCEA), in terms of tissue-specific targeting for gene therapy. The promoter was subcloned to a luciferase reporter gene (pCEA/Luc) in our laboratory and compared with a virally controlled luciferase vector (pSV40/Luc). METHODS: Four human cancer cell lines (HeLa, SW480, Caco2, and SW1116) were transfected with either pCEA/Luc or pSV40/Luc. Cells were treated with interferon-gamma and assayed at 72 hours after treatment. Carcinoembryonic antigen level was measured by enzyme immunoassay. Luciferase expression was measured at 48 hours and one week after transfection by luminometry. RESULTS: Luciferase activity after transfection with pCEA/Luc was higher in CEA-positive cells than in CEA-negative cells (P < 0.0001). pCEA/Luc demonstrated higher activity than pSV40/Luc in CEA-positive cells (P < 0.0001), but not in CEA-negative cells. In Caco2 cells, which before confluence are CEA-negative, luciferase expression increased on reaching confluence (P < 0.0001). Well to moderately differentiated cells responded to the interferon-gamma treatment, but the increase in CEA secretion did not correspond to an increase in pCEA/Luc expression. CONCLUSIONS: The expression of pCEA correlates well with the CEA production by the specific cell line offering a potential tissue-specific targeting strategy for colon cancer gene therapy. Furthermore, the tissue-specific CEA promoter has a higher and more persistent activity in CEA-positive human cancer cells than a viral promoter. The lack of response to interferon-gamma treatment suggests a different mechanism of action for interferon-gamma other than directly interacting with the promoter.

Carcinoembryonic Antigen↗
PubMed1996

Functional evidence for a colorectal cancer tumor suppressor gene at chromosome 8p22-23 by monochromosome transfer.

Chromosome 8p is considered, from loss of heterozygosity analysis, to be a strong candidate for the location of a tumor suppressor gene inactivated in colorectal cancer. We have found a 53% (27 of 51) rate of allelic loss at the LPL locus on 8p22, with the smallest region of overlap of deletions including the region D8S258 to D8S277. Using microcell-mediated monochromosome 8 transfer into three colorectal cancer cell lines, SW480, SW620 and HT29, we have demonstrated a reduction of tumorigenicity in SW620 hybrids. Partial deletions of chromosome 8 in some SW620/8 hybrids further delineate the critical region(s) to 8p22-23. Hybrids of the colorectal cancer cell lines SW480 and HT29 containing chromosome 8 did not show suppression of tumorigenesis, but the H29/8 hybrid showed total suppression of soft agar clonicity. This indicates an alternate pathway of mutational progression in these three lines, despite the fact that SW480 was derived from the same patient as SW620.

Adenoma↗
PubMed1997

[Application of subtractive hybridization in screening for colorectal cancer negatively related genes].

OBJECTIVE: To search previously uncertained factors that corelated with the occurence and development of human colorectal cancer. METHOD: Subtractive hybridization technique was employed to screen down-regulated genes of colorectal cancer. RESULTS: We obtained 46 clones which highly were expressed in normal intestinal mucosa but much lower or none in colorectal cancer. Two of the 46 clones, SCN6 and SCN19, were accepted by the Genbank Database as novel genes with the accession numbers U17714 and U20248. Full length cDNA (2932bp) of SNC6 was sequenced, and supposed to encode a protein comprised 271 amino acids, MW30kd, which shared less than 30% homology with the protein database. The gene was localized to human chromosome 22q13. RNA dot blot analysis showed that the expression level of SNC6 was lower in colorectal cancer than in normal intestinal mucosa, and similar results were found in breast cancer. Northern blot showed higher expression levels of SNC6 in liver, lung, prostate, testis, ovary and K562 cell line than in other tissues. CONCLUSION: SNC6 can be further investigated as a novel colorectal cancer negatively related gene.

Colonic Neoplasms↗
PubMed2004

Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk.

The MutY human homologue (MYH) gene encodes a member of the base excision repair pathway that is involved in repairing oxidative damage to DNA. Two germline MYH gene mutations that result in Myh proteins containing amino acid substitutions Y165C and G382D (hereafter called the Y165C and G382D mutations) are associated with adenomatous poly-posis and colorectal cancer among patients from several European poly-posis registries. We used a population-based series of 1238 colorectal cancer patients and 1255 healthy control subjects from Ontario, Canada, to examine the risk of colorectal cancer among biallelic and monoallelic germline MYH Y165C and G382D mutation carriers. The entire MYH gene coding region was screened in all MYH Y165C and G382D mutation carriers. Compared with noncarriers, biallelic and monoallelic germline MYH gene mutation carriers had an increased risk of colorectal cancer and were more likely to have first-or second-degree relatives with colorectal cancer (relative risk = 1.54, 95% confidence interval = 1.10 to 2.16). The increased risk of colorectal cancer in biallelic and monoallelic MYH gene mutation carriers was not consistently associated with the development of multiple adenomatous polyps. Loss of heterozygosity in at least one of four loci in MYH was detected in eight (47%) of 17 colorectal tumors from monoallelic MYH gene mutation carriers but in only two (20%) of 10 colorectal tumors from biallelic MYH gene mutation carriers. These two MYH gene mutations may account for a substantial fraction of hereditary colorectal cancer.

Adenomatous Polyposis Coli↗