PHENOTYPIC CHARACTERISTICS OF HEREDITARY NON-POLYPOSIS COLORECTAL CANCER BY THE AMSTERDAM CRITERIA: AN ASIAN PERSPECTIVE

2008 ◽  
Vol 78 (7) ◽  
pp. 556-560 ◽  
Author(s):  
Min-Hoe Chew ◽  
Poh-Koon Koh ◽  
Kheng-Hong Ng ◽  
Jit-Fong Lim ◽  
Kok-Sun Ho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phenotypic Characteristics ◽  
Amsterdam Criteria

scholarly journals Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abram Bunya Kamiza ◽  
Wen-Chang Wang ◽  
Jeng-Fu You ◽  
Reiping Tang ◽  
Huei-Tzu Chien ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Cumulative Risk ◽  
Germline Mutations ◽  
Han Chinese ◽  
Chinese Patients ◽  
Mutation Carriers ◽  
Amsterdam Criteria ◽  
Cumulative Risks ◽  
Age And Sex

AbstractPatients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

Genetic testing is important in families with a history suggestive of hereditary non-polyposis colorectal cancer even if the Amsterdam criteria are not fulfilled

1997 ◽  
Vol 84 (2) ◽  
pp. 233-237 ◽  
Author(s):  
N. E. Beck ◽  
I. P. M. Tomlinson ◽  
T. Homfray ◽  
S. V. Hodgson ◽  
C. J. Harocopos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Testing ◽  
Amsterdam Criteria

scholarly journals Performance of tumor testing for Lynch syndrome identification in patients with colorectal cancer: A retrospective single-center study

2018 ◽  
Vol 105 (1) ◽  
pp. 76-83 ◽  
Author(s):  
Stefano Signoroni ◽  
Maria Grazia Tibiletti ◽  
Maria Teresa Ricci ◽  
Massimo Milione ◽  
Federica Perrone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Characteristic Curve ◽  
Age At Onset ◽  
Area Under The Curve ◽  
Single Center ◽  
Germline Variants ◽  
Amsterdam Criteria ◽  
Clinicopathologic Parameters ◽  
Msi Analysis

Objective: To investigate the performance of tumor testing approaches in the identification of Lynch syndrome (LS) in a single-center cohort of people with colorectal cancer (CRC). Methods: A retrospective analysis of data stored in a dedicated database was carried out to identify patients with CRC suspected for LS who were referred to Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, between 1999 and 2014. The sensitivity and specificity of immunohistochemistry (IHC) for mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis (alone or combined) were calculated with respect to the presence of causative MMR germline variants. Results: A total of 683 patients with CRC suspected for LS were identified. IHC results of MMR protein analysis and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis was performed in 418 patients based on the IHC or MSI test result and/or clinical features. Univariate and multivariate analysis revealed a significant correlation of pathogenic MMR germline variants with all clinicopathologic features including Amsterdam criteria, presence of endometrial cancer, CRC site, age at onset, stage, and grade. The highest odds ratio values were observed for IHC and MSI (17.1 and 8.8, respectively). The receiver operating characteristic curve and area under the curve values demonstrated that IHC alone or combined with other clinicopathologic parameters was an excellent test for LS identification. Conclusions: This study confirms the effectiveness of tumor testing to identify LS among patients with CRC. Although IHC and MSI analysis were similarly effective, IHC could be a better strategy for LS identification as it is less expensive and more feasible.

Immunohistochemistry Identifies Carriers of Mismatch Repair Gene Defects Causing Hereditary Nonpolyposis Colorectal Cancer

2005 ◽  
Vol 23 (21) ◽  
pp. 4705-4712 ◽  
Author(s):  
Astrid T. Stormorken ◽  
Inger Marie Bowitz-Lothe ◽  
Tove Norèn ◽  
Elin Kure ◽  
Steinar Aase ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Predictive Values ◽  
Blood Samples ◽  
Bethesda Criteria ◽  
Amsterdam Criteria ◽  
Hereditary Nonpolyposis

Purpose Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by mutations in mismatch repair (MMR) genes. The aim of this study was to validate immunohistochemistry and family history as prescreening tools to predict germline mutations in MLH1, MSH2, and MSH6. Patients and Methods Pedigrees from 250 families were extended, cancer diagnoses were verified, and families were classified according to the Amsterdam and the Bethesda criteria. Tumor specimens were examined with immunohistochemistry for the presence of MLH1, MSH2, and MSH6 proteins. Mutation analyses were performed in blood samples from the same patients. Results Blood samples from affected index persons in 181 families and tumor specimens from 127 of the affected index persons were obtained. Thirty tumors lacked one or more gene products. Sensitivity of immunohistochemistry to detect mutation carriers was 100%, specificity was 82%, and positive predictive value was 85%. Sensitivities, specificities, and positive predictive values for the Amsterdam criteria were 82%, 8%, and 45%, respectively, and for the Bethesda criteria were 100%, 0%, and 48%, respectively. Distribution of mutations was MLH1 = 4, MSH2 = 11, and MSH6 = 4. Conclusion Wide clinical criteria to select HNPCC kindreds, followed by immunohistochemistry of tumor material from one affected person in each family, had high sensitivity and specificity to predict MMR mutations.

scholarly journals Frequency of replication errors in colorectal cancer and their association with family history

Gut ◽  
1998 ◽  
Vol 43 (4) ◽  
pp. 553-557 ◽  
Author(s):  
S R Brown ◽  
P J Finan ◽  
L Cawkwell ◽  
P Quirke ◽  
D T Bishop
Keyword(s):  
Colorectal Cancer ◽  
Family History ◽  
Mutation Status ◽  
Replication Errors ◽  
Cancer Group ◽  
Amsterdam Criteria ◽  
History Of ◽  
Regional Population ◽  
Colorectal Cancer Patients

Background—Replication errors (RERs) characterise tumours of hereditary non-polyposis colorectal cancer (HNPCC). RER status may therefore improve identification of such families previously diagnosed by family history alone.Aims—To assess RER and HNPCC frequency within a population of colorectal cancer patients and a regional population of family history defined (Amsterdam criteria) HNPCC families.Methods—Family history was assessed by personal interview in a population of 479 patients with colorectal cancer attending one follow up clinic. Seven fluorescently labelled microsatellites were used to investigate RER frequency in colorectal cancers from 89 patients of this population with varying degrees of family history and 20 Amsterdam criteria positive families (four with a known germline mutation, 16 with unknown mutation status) from the regional population.Results—Only four of the follow up population (0.8%) came from families meeting the Amsterdam criteria with only one showing RERs. The frequency of RERs was similar in the early onset cancer group (less than 50 years of age), those with a family history, and those with no family history of colorectal cancer. From the regional population, RERs were identified in 4/4 families with a mutation but only 8/16 families with unknown mutation status.Conclusions—No correlation was seen between RER status and strength of family history except in HNPCC families. Results also indicate that half of the Amsterdam criteria defined families do not exhibit RERs, perhaps suggesting a different mechanism of tumorigenesis.

Who Should Be Sent for Genetic Testing in Hereditary Colorectal Cancer Syndromes?

2007 ◽  
Vol 25 (23) ◽  
pp. 3534-3542 ◽  
Author(s):  
Henry T. Lynch ◽  
C. Richard Boland ◽  
Miguel A. Rodriguez-Bigas ◽  
Christopher Amos ◽  
Jane F. Lynch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Testing ◽  
Hereditary Colorectal Cancer ◽  
Genetic Counselors ◽  
Amsterdam Criteria ◽  
Syndrome Diagnosis ◽  
Hereditary Colorectal Cancer Syndromes ◽  
Informative Family ◽  
Peutz Jeghers Syndrome ◽  
Cancer Syndromes

Genetic testing is being adopted increasingly to identify individuals with germline mutations that predispose to hereditary colorectal cancer syndromes. Deciding who to test and for which syndrome is of concern to members of the GI oncology community, molecular geneticists, and genetic counselors. The purpose of this review is to help provide guidelines for testing, given that the results influence syndrome diagnosis and clinical management. Although family history may determine whether testing is appropriate and may direct testing to the most informative family member, evolving clinicopathologic features can identify individual patients who warrant testing. Thus, although the usual absence of clinical premonitory signs in hereditary nonpolyposis colorectal cancer (or Lynch syndrome) adds difficulty to its diagnosis, use of the Amsterdam Criteria and Bethesda Guidelines can prove helpful. In contrast, premonitory stigmata such as pigmentations in Peutz-Jeghers syndrome and the phenotypic features of familial adenomatous polyposis aid significantly in syndrome diagnosis. We conclude that the physician's role in advising DNA testing is no small matter, given that a hereditary cancer syndrome's sequelae may be far reaching. Genetic counselors may be extremely helpful to the practicing gastroenterologist, oncologist, or surgeon; when more specialized knowledge is called for, referral can be made to a medical geneticist and/or a medical genetics clinic.

Impact of colonoscopy screening on individuals at high risk of hereditary nonpolyposis colorectal cancer (HNPCC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 384-384
Author(s):  
C. Guillen-Ponce ◽  
C. Martinez-Sevila ◽  
R. Jover ◽  
R. Perea ◽  
M. Molina-Garrido ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Early Stage ◽  
Colorectal Adenomas ◽  
Medical Documentation ◽  
Synchronous Tumors ◽  
Colonoscopy Screening ◽  
Amsterdam Criteria ◽  
The Impact

384 Background: Colonoscopy screening reduces the incidence of, and mortality from, colorectal cancer (CRC) in individuals with HNPCC. The aim of this study was to determine the impact of colonoscopic follow-up in individuals at high risk of HNPCC, in terms of detection of precursor lesions (adenomas) or cancer. Methods: Between 2005-2008, 163 individuals with HNPCC were advised to undergo regular follow-up colonoscopy. Compliance and results of the scans were evaluated annually and were verified with medical documentation. Results: Of the 125 individuals who underwent at least one colonoscopy during the follow-up period of colonoscopy screening, in 33 subjects (26%) at least one colonic adenoma was detected. The median number of adenomas detected per colonoscopy in individuals with polyps was 2. The number of colonoscopies with polyps did not differ between women and men. However, the number of polyps removed by colonoscopy and the total number of polyps removed during the follow-up period was significantly higher in men (p = 0.005, p = 0.05 bilateral, respectively). 5 individuals (4%) were diagnosed with CRC, one of whom had two synchronous tumors. Of these, four individuals had properly followed the screening recommendations with the recommended frequency. In the case where two synchronous tumors were detected, it was the first colonoscopy screening that had been performed on the individual. None had had cancer previously, they were healthy relatives of an index case. All except one belonged to families that fulfilled the Amsterdam criteria I / II. All the tumors were diagnosed at an early stage, except two, which exhibited positive nodes. Conclusions: Colonoscopy screening is effective in diagnosing colorectal adenomas and cancer in individuals with HNPCC. Men with HNPCC have a greater number of colorectal adenomas. Screening allows the detection of colorectal cancer at an early stages. Funded by a young researcher's grant from the Spanish Society of Medical Oncology 2006. No significant financial relationships to disclose.

scholarly journals Report of a Novel Mutation inMLH1Gene in a Hispanic Family from Puerto Rico Fulfilling Classic Amsterdam Criteria for Lynch Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Juan M. Marqués-Lespier ◽  
Yaritza Diaz-Algorri ◽  
Maria Gonzalez-Pons ◽  
Marcia Cruz-Correa
Keyword(s):  
Colorectal Cancer ◽  
Puerto Rico ◽  
Lynch Syndrome ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Limited Information ◽  
Protein Coding ◽  
Genetic Sequencing ◽  
Amsterdam Criteria ◽  
Hispanic Family

In Puerto Rico, colorectal cancer (CRC) represents the second leading cause of cancer in men and women. Familial CRC accounts for 10–15% of the total CRC cases, while Lynch syndrome accounts for approximately 2–4% of cases. Limited information is available about the prevalence, clinical manifestations, and genetic mutations of hereditary CRC in US Hispanic individuals. In this paper we report a novel mutation in thehMLH1gene in a Puerto Rican Hispanic family with Lynch syndrome recruited through the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). Our proband was identified by applying Amsterdam and Bethesda criteria for Lynch syndrome, analysis of protein expression by immunohistochemistry, and genetic sequencing of the mismatch repair genes. A novel mutation at c.2044_2045 inhMLH1consisting of the deletion of two consecutive nucleotides (AT) at exon 18 was identified. This deletion causes a frameshift in the protein coding sequence at p.682 resulting in premature termination and a truncated MLH1 protein. To our knowledge, this mutation has not been previously reported in the literature. The detection of this novel mutation inMLH1further emphasizes the need for genetic testing in at-risk patients for hereditary CRC from various ethnic and racial backgrounds.

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