scholarly journals The T/G mutation in exon 8 of HMSH2 gene in the sporadic colon cancer patients

2006 ◽  
Vol 53 (2) ◽  
pp. 57-60
Author(s):  
Eva Langner ◽  
Karolina Przybyzowska ◽  
Galbfach Przemyszaw ◽  
Janusz Kunierz ◽  
Beata Smolarz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Histological Grade ◽  
Clinical Parameters ◽  
Dna Mismatch ◽  
Mmr Genes ◽  
Significant Difference ◽  
Hereditary Nonpolyposis ◽  
Sporadic Colon Cancer ◽  
The Relationship

The DNA mismatch repair (MMR) system guards against genomic instability, therefore the mutations in the human MMR genes cause the majority of the hereditary nonpolyposis colorectal cancer (HNPCC) and a small percentage of the sporadic colon cancer. hMSH2 is one of MMR genes involved in the correction of mispairing during replication and its mutations are associated with both - microsatellite instability and the hereditary and sporadic colon tumor genesis. The aim of this study was to analyze the T/G mutation (codon 458) in exon 8 of hMSH2 gene in the sporadic colon cancer cells. We also examined the relationship between the T/G mutation of hMSH2 gene, and the selected prognostic factors such as Dukes? stage, histological grade and lymph node metastasis. We analyzed samples of tumor from 75 patients with sporadic colorectal cancers. The mutation in the hMSH2 gene ware determined by the RFLP-PCR. We found T/G mutation in exon 8 of hMSH2 gene in 5 patients (6,7%). There was no statistically significant difference between this mutation and selected clinical parameters. The results of our studies revealed that mutations of hMSH2 gene may lead to development of colorectal cancer. No dependence between the mutation of hMSH2 gene and clinical parameters, suggests that the mutation of hMSH2 gene may have a critical significance for the first steps of carcinogenesis in colon epithelial.

Altered Expression of MLH1, MSH2, and MSH6 in Predisposition to Hereditary Nonpolyposis Colorectal Cancer

2003 ◽  
Vol 21 (19) ◽  
pp. 3629-3637 ◽  
Author(s):  
Elise Renkonen ◽  
Yange Zhang ◽  
Hannes Lohi ◽  
Reijo Salovaara ◽  
Wael M. Abdel-Rahman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Population Based ◽  
Altered Expression ◽  
Dna Mismatch ◽  
Mmr Genes ◽  
Hereditary Nonpolyposis

Purpose: A considerable fraction (30% to 70%) of families with verified or putative hereditary nonpolyposis colorectal cancer fails to show mutations in DNA mismatch repair (MMR) genes. Our purpose was to address the genetic etiology of such families. Materials and Methods: We scrutinized a population-based cohort of 26 families from Finland that had screened mutation-negative by previous techniques. Blood was tested for allelic messenger RNA (mRNA) expression of MLH1, MSH2, and MSH6 by single nucleotide primer extension (SNuPE), and tumor tissue for MMR protein expression by immunohistochemistry (IHC) as well as for microsatellite instability (MSI). Full-length cDNAs of genes implicated by SNuPE or IHC were cloned and sequenced. Results: Unbalanced mRNA expression of MLH1 alleles was evident in two families. An inherited nonsense mutation was subsequently identified in one family, and complete silencing of the mutated allele was identified in the other family. Extinct protein expression by IHC implicated MLH1 in these two and in four other families, MSH2 in four families, and MSH6 in one family. Although no unequivocal genomic mutations were detected in the latter families, haplotype and other findings provided support for heritable defects. With one exception, all tumors with IHC alterations showed MSI, in contrast to the remaining families, which showed neither IHC changes nor MSI. Conclusion: Our expression-based strategy stratified the present “mutation-negative” cohort into two discrete categories: families linked to the major MMR genes MLH1, MSH2, and MSH6 (11 [42%] of 26) and those likely to be associated with other, as yet unknown susceptibility genes (15 [58%] of 26).

scholarly journals Clinical and genetic aspects of differential diagnostics of hereditary non-polyposis colorectal cancer

2019 ◽  
Vol 6 (2) ◽  
pp. 21-27
Author(s):  
A. V. Semyanikhina ◽  
A. O. Rasulov ◽  
L. N. Lyubchenko
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Heterogeneous Group ◽  
Differential Diagnostics ◽  
Genetic Characteristics ◽  
Dna Mismatch ◽  
Mmr Genes ◽  
Long Time

Lynch syndrome was synonymous with hereditary non-polyposis colorectal cancer for a long time, however, mapping of the DNA mismatch repair (MMR) genes has led to distinguish Lynch syndrome as an independent syndromic unit from a number of Lynch-like syndromes that phenotypically mimic with the most frequent hereditary variant of colon cancer but genetically representing quite a heterogeneous group. This article presents up to date clinical and genetic characteristics of Lynch syndrome and Lynch-like conditions.

scholarly journals Systemic therapy for colorectal cancer

2003 ◽  
Vol 11 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Borut Stabuc
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Metastatic Colorectal Cancer ◽  
Adjuvant Treatment ◽  
Randomized Clinical Trials ◽  
Response Rate ◽  
Phase Iii ◽  
Oral Fluoropyrimidines ◽  
Significant Difference

Colorectal cancer alone accounts for around 200,000 deaths in Europe and represents a significant health problem. Although about fifty percent of patients are cured by surgery alone, the other half will eventually die due to metastatic disease, which includes approximately 25% of patients who have evidence of metastases at the time of diagnosis. Surgical resection of the primary tumor and regional lymph nodes is the only curative therapy for colorectal cancer. However, adjuvant chemotherapy in stage III for colon cancer following curative resection has been shown to reduce the risk of recurrence by 19-40% and of death by 16-33%. Today, 5-fluoroUracil and Leucovorin given for six months may represent the best adjuvant treatment available The contribution of levamisole to adjuvant treatment seems to be marginal, if any. The benefit of adjuvant chemotherapy for the patients with Dukes B colon cancer is less clear. A meta-analysis of 1,381 patients with advanced colorectal cancer showed a significant increase in response rate with the bolus 5-fluoroUracil and Leucovorin versus 5-fluoroUracil alone but no significant difference in median survival. Continuous infusion allows higher doses of 5-FU than rapid bolus infusion and improves response rate survival and time to progression. Oral fluoropyrimidines (capecitabine and Uracil/Tegafur [UFT]) are as active as intravenous fluoropyrimidines. Compared to intravenous 5FU, oral fluoropyrimidines have safety advantages clinical benefits, and are more convenient for patients. Phase III randomized clinical trials in patients with metastatic colorectal cancer demonstrate the significant superiority of combining irinotecan with 5-fluoroUracil and Leucovorin or oxaliplatin with 5-fluoroUracil and Leucovorin over the same 5-fluoroUracil and Leucovorin alone. Several phase II studies have shown that the combination of the oral fluoropyrimidines plus irinotecan or oxaliplatin is very active in metastatic colorectal cancer. Trials with agents acting on novel targets in colorectal cancer are progressing rapidly, including doxifluridine, new inhibitors of thymidylate synthase (ZD9331), oral camptothecins (Rubitecan), multitarget antifolate antimetabolite (Premetrexet), inhibitors of epidermal growth factor receptor (Cetuximab), COX-2 inhibitors (celecoxib) and farnesyltransferaze inhibitors (Zarnestra). However, a few randomized trials failed to show a survival advantage compared with placebo in patients with advanced refractory colorectal cancer.

scholarly journals A Dynamic Family History model Of Hereditary Nonpolyposis Colorectal Cancer and Critical Illness Insurance

2007 ◽  
Vol 2 (2) ◽  
pp. 289-325 ◽  
Author(s):  
L. Lu ◽  
A. S. Macdonald ◽  
H. R. Waters ◽  
F. Yu
Keyword(s):  
Colorectal Cancer ◽  
Critical Illness ◽  
Family History ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Familial Aggregation ◽  
Family History Information ◽  
Dna Mismatch ◽  
Genetic Test Results ◽  
Hereditary Nonpolyposis ◽  
History Of

ABSTRACTHereditary nonpolyposis colorectal cancer (HNPCC) is characterised by the familial aggregation of cancer of the colon and rectum (CRC). It may be caused by any of five mutations in DNA mismatch repair (MMR) genes or by non-genetic factors, such as life style. However, it accounts for only about 2% of CRC, which is a very common cancer. Previous actuarial models, of diseases with only genetic causes, assumed that a family history of the disease shows mutations to be present, but this is not true of HNPCC. This is a significant limitation, since the best information available to an underwriter (especially if the use of genetic test results is banned) is likely to be knowledge of a family history of CRC. We present a Markov model of CRC and HNPCC, which includes the presence of a family history of CRC as a state, and estimate its intensities allowing for MMR genotype. Using this we find the MMR mutation probabilities for an insurance applicant with a family history of CRC. Our model greatly simplifies the intensive computational burden of finding such probabilities by integrating over complex models of hidden family structure. We estimate the costs of critical illness insurance given the applicant's genotype or the presence of a family history. We then consider what the cost of adverse selection might be, if insurers are unable to use genetic tests or family history information. We also consider the effect of using alternative definitions of a family history in underwriting.

scholarly journals Advanced Colon Cancer Before the Age of 20 Years: A Case for Extension of the Current Colonscopy Surveillance Guidelines in Hereditary Nonpolyposis Colorectal Cancer Syndrome

2004 ◽  
Vol 18 (5) ◽  
pp. 319-320 ◽  
Author(s):  
Victor K Wong ◽  
Eric M Yoshida ◽  
Anthony G Ryan ◽  
Stephen GF Ho ◽  
Baljinder Salh
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Pelvic Mass ◽  
Cancer Syndrome ◽  
Advanced Colon Cancer ◽  
Hereditary Nonpolyposis ◽  
History Of ◽  
Current Guidelines ◽  
Colorectal Adenocarcinomas

BACKGROUND:Hereditary nonpolyposis colorectal cancer (HNPCC) currently accounts for between 2% to 6% of all colorectal adenocarcinomas. Controversies exist regarding the current guidelines for colonoscopic screening for colon cancer.CASE REPORT:A case of colon cancer in a young Japanese man with a family history of colon cancer that did not meet the criteria for HNPCC is reported. A malignant pelvic mass discovered shortly before his 20th birthday prompted a colonoscopy. The findings at colonscopy determined that the patient and his family fulfilled the criteria of HNPCC.CONCLUSION:Before finding a pelvic mass metastatic from adenocarcinoma of the ascending colon, this patient was clearly outside of the current guidelines for HNPCC screening. It is suggested that in similar patients, even if they do not fulfill all the criteria for HNPCC, it would be appropriate to consider screening well before the recommended lower age.

Adjuvant chemotherapy with uracil-tegafur (UFT) for stage III colorectal cancer: Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4049-4049 ◽  
Author(s):  
T. Hamaguchi ◽  
K. Shirao ◽  
Y. Moriya ◽  
S. Yoshida ◽  
S. Kodaira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Hazard Ratio ◽  
Stage Iii ◽  
Control Group ◽  
Significant Difference ◽  
Resected Stage

4049 Background: In the latter 1990s, no consensus was reached as to whether adjuvant chemotherapy was standard treatment for completely resected stage III colorectal cancer in Japan. At that time, we started two randomized controlled trials to clarify the role of adjuvant chemotherapy of stage III colon and rectal cancer in the same time. Methods: Patients with completely resected stage III cancer of the colon or rectum (PS, 0 to 2; age, 20 to 75 years; no other adjuvant therapy) were eligible for these trials. Patients were registered within 6 weeks after surgery and were randomly assigned to receive surgery alone (control group) or surgery followed by treatment with UFT (400 mg/m2/day), given for 5 consecutive days per week for 1 year (UFT group). The target number of patients was 500 for colon cancer and 400 for rectal cancer (hazard ratio = 0.67, one-sided a= 0.05, β= 0.2). The primary endpoint was relapse-free survival (RFS), and the secondary end point was overall survival (OS). Results: Between October 1996 and April 2001, a total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. Four ineligible patients were excluded; data from the remaining 332 patients with colon cancer and 274 with rectal cancer were analyzed. The patients’ characteristics were similar in the groups. Analysis of the results of follow-up until March 2006, at least 5 years after surgery in all patients (median follow-up period, 6.2 years), showed no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the control group. The only grade 4 toxicity was diarrhea, occurring in 1 patient with colon cancer and 1 patient with rectal cancer. Conclusions: Postoperative adjuvant chemotherapy with UFT is well tolerated and improved RFS and OS in patients with stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.67). [Table: see text] No significant financial relationships to disclose.

Development and validation of a robust prognostic and predictive signature for colorectal cancer (CRC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4036-4036
Author(s):  
A. M. Glas ◽  
P. Roepman ◽  
R. Salazar ◽  
G. Capella ◽  
V. Moreno ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Gene Signature ◽  
Low Risk ◽  
Stage Ii ◽  
Significant Difference ◽  
Independent Cohort

4036 Background: Between 25 and 35% of stage II CRC patients will experience a recurrence of their disease and may benefit from adjuvant chemotherapy. Official guidelines give suggestions but no clear recommendation for best risk stratification. Here we describe the development a robust signature that predicts disease relapse and can assist in treatment decisions. Methods: Fresh frozen tumor tissues from 180 patients with stage I, II and III colorectal cancer undergoing surgery were analyzed using high density Agilent 44K oligonucleotide arrays. Median FU was 70.2 months; 85% of patients did not receive adjuvant chemotherapy. Unsupervised hierarchical clustering based on full-genome gene expression measurement indicated the existence of 3 main colon molecular subclasses. Survival analysis of the 3 classes showed that subtype C (n= 27) had a poor outcome and subtype A (n= 48) good outcome. Only the intermediate group B (n=104) was used to develop a signature by using a cross validation procedure to score all genes for their association with 5-yr distant metastasis free survival (DMFS) and subsequently applied to all samples (n=180). The obtained gene signature was further validated on an independent cohort of 178 stage II + III colon samples. Results: A set of 38 prognosis related gene probes showed robust DMFS association in over 50% of all iterations in the Training Set of 180 samples. The gene signature was validated on an independent cohort of 178 samples from stage II + III colon cancer patients. The profile classified 61% of the validation samples as low-risk and 39% as high-risk. The low- and high-risk samples showed a significant difference in DMFS with a HR of 3.19 (P= 8.5e-4). Five-year DMFS rates were 89% (95%CI 83–95) for low-risk and 62% (95%CI 50–77) for high-risk samples. Moreover, the profile showed a significant performance within stage II (P=0.0058) and III (P=0.036) only samples. The performance of the profile was significant for both untreated (P=0.0082) and treated patients (P=0.016) suggesting that its power is independent of treatment benefits. Conclusions: ColoPrint is able to predict the prognosis of stage II and III colon cancer patients and facilitates the identification of patients who would benefit from adjuvant chemotherapy. [Table: see text]

Effect of young age (<50) on clinical, pathologic features and survival of patients with colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14025-e14025
Author(s):  
Jamal Zidan ◽  
Jehad Abu Salah ◽  
Adi Sharabi-Nov
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Medical Center ◽  
Young Patients ◽  
Young Group ◽  
Old Patients ◽  
Pathological Characteristics ◽  
Pathologic Features ◽  
Number Of Patients ◽  
Significant Difference

e14025 Background: Colorectal cancer is one of the most common malignancies in both men and women in Israel. Most patients with colon cancer are older than 50 years of age. However young patients are not rare. There is no consensus in the literature regarding the behavior of this disease in young patients. Clinical and pathological characteristics of colon cancer patients treated at Oncology Institute in Ziv Medical Center were retrospectively analyzed. The aim of the present study is to compare clinical and pathological features of colon cancer between young and old patients. Methods: A total of 200 patients with colon cancer were treated at our institute during 8 years. Twenty five (12.5%) of them were <50 years age (young patients) at diagnosis. All clinical and pathological characteristics were taken retrospectively from the hospital files. In situations where the pathological findings were not noted in the chart, review of the stored tumor was requested from the pathology department. Acceptable statistical methods were used for statistical calculations. Results: Among the 200 patients 25 (12.5%) were <50 years age at diagnosis (mean age 41 years) and 175 were >50 years (mean age 70 years). Males were 56% of the young group and 60.1% of the old one. Arab patients were 52% of the young and only 12.6% of the old group although total number of Arabs was 35 of 200 patients. No significant difference was found in stage of tumor at diagnosis between the young group (YG) and the old group (OG). Twenty percent of YG had distant metastases compared to 26.5% in the OG. Histopathological grade 3 tumors were found in 33.3% of the YG versus 7.7% in the OG. Surgery and chemotherapy were done in 96% and 88% in YG versus 95.4% and 69.7% in the OG respectively. In a median follow up period of 96 months 35% of young patients died of their disease compared to 33.1% of the old patients. Conclusions: Young patients with colon cancer were diagnosed at the same stage of the disease as old patients. More tumors were high grade in YG. More patients were candidates for chemotherapy in the YG. Significantly more Arab patients were young at the time of diagnosis than Jewish patients. Further studies with higher number of patients are suggested to clarify our findings.

Sign in / Sign up

Export Citation Format

Share Document