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.

Genotype-Phenotype Comparison of German MLH1 and MSH2 Mutation Carriers Clinically Affected With Lynch Syndrome: A Report by the German HNPCC Consortium

2006 ◽  
Vol 24 (26) ◽  
pp. 4285-4292 ◽  
Author(s):  
Timm Goecke ◽  
Karsten Schulmann ◽  
Christoph Engel ◽  
Elke Holinski-Feder ◽  
Constanze Pagenstecher ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Germline Mutations ◽  
Time Span ◽  
Msh2 Mutation ◽  
Mutation Carriers ◽  
Phenotype Comparison ◽  
Rectal Cancers ◽  
Prostate Cancers ◽  
Colorectal Cancer Patients

Purpose Lynch syndrome is linked to germline mutations in mismatch repair genes. We analyzed the genotype-phenotype correlations in the largest cohort so far reported. Patients and Methods Following standard algorithms, we identified 281 of 574 unrelated families with deleterious germline mutations in MLH1 (n = 124) or MSH2 (n = 157). A total of 988 patients with 1,381 cancers were included in this analysis. Results We identified 181 and 259 individuals with proven or obligatory and 254 and 294 with assumed MLH1 and MSH2 mutations, respectively. Age at diagnosis was younger both in regard to first cancer (40 v 43 years; P < .009) and to first colorectal cancer (CRC; 41 v 44 years; P = .004) in MLH1 (n = 435) versus MSH2 (n = 553) mutation carriers. In both groups, rectal cancers were remarkably frequent, and the time span between first and second CRC was smaller if the first primary occurred left sided. Gastric cancer was the third most frequent malignancy occurring without a similarly affected relative in most cases. All prostate cancers occurred in MSH2 mutation carriers. Conclusion The proportion of rectal cancers and shorter time span to metachronous cancers indicates the need for a defined treatment strategy for primary rectal cancers in hereditary nonpolyposis colorectal cancer patients. Male MLH1 mutation carriers require earlier colonoscopy beginning at age 20 years. We propose regular gastric surveillance starting at age 35 years, regardless of the familial occurrence of this cancer. The association of prostate cancer with MSH2 mutations should be taken into consideration both for clinical and genetic counseling practice.

scholarly journals Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk

2015 ◽  
Vol 33 (4) ◽  
pp. 319-325 ◽  
Author(s):  
Sanne W. ten Broeke ◽  
Richard M. Brohet ◽  
Carli M. Tops ◽  
Heleen M. van der Klift ◽  
Mary E. Velthuizen ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Lynch Syndrome ◽  
Family Members ◽  
Cumulative Risk ◽  
Mismatch Repair Gene ◽  
Genetic Modifiers ◽  
Analysis Model ◽  
Repair Gene ◽  
Mutation Carriers ◽  
Significant Difference

Purpose The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. Methods Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome–associated cancers. Results The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P < .001). Significant SIRs were observed for cancers of the small bowel, ovaries, breast, and renal pelvis. Conclusion CRC and EC risks were found to be markedly lower than those previously reported for the other MMR. However, these risks embody the isolated risk of carrying a PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks.

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.

Efficacy of proximal colectomy for surgical management of right-sided first colorectal cancer in Lynch Syndrome mutation carriers

2018 ◽  
Vol 216 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Molly J. Hiatt ◽  
Murray Joseph Casey ◽  
Henry T. Lynch ◽  
Carrie L. Snyder ◽  
Mark Stacey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Surgical Management ◽  
Mutation Carriers

scholarly journals Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome

2012 ◽  
Vol 30 (35) ◽  
pp. 4409-4415 ◽  
Author(s):  
Christoph Engel ◽  
Markus Loeffler ◽  
Verena Steinke ◽  
Nils Rahner ◽  
Elke Holinski-Feder ◽  
...  
Keyword(s):  
Small Bowel ◽  
General Population ◽  
Lynch Syndrome ◽  
Cox Regression ◽  
Incidence Rates ◽  
Cancer Surveillance ◽  
Cox Regression Analysis ◽  
Mutation Carriers ◽  
Cumulative Risks ◽  
The Impact

Purpose Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6. Patients and Methods Data were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex- and MMR gene–specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk. Results The cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers. Conclusion The sex- and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome.

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.

Mismatch Repair Genes and EPCAM germline mutations in patients with gastric or colorectal cancer with suspected of Lynch syndrome.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e13623-e13623 ◽  
Author(s):  
Nora Manoukian Forones ◽  
Fernanda Tereza Lima ◽  
Renan Paulo Martin ◽  
Leonardo Martins ◽  
Patricia Valera Lima Teixeira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Germline Mutations ◽  
Mismatch Repair Genes ◽  
Repair Genes

scholarly journals Lynch syndrome I: A case report

2008 ◽  
Vol 61 (1-2) ◽  
pp. 79-82
Author(s):  
Vesna Zivkovic ◽  
Vuka Katic ◽  
Jasmina Gligorijevic ◽  
Zlatibor Andjelkovic ◽  
Aleksandar Petrovic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Case Report ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Clinical Stage ◽  
Family Members ◽  
Advanced Rectal Cancer ◽  
Degree Relative ◽  
Mmr Genes ◽  
Amsterdam Criteria

Introduction. Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndromes J and II, accounts for about 5-8% of colorectal cancers. Lynch syndrome I is an autosomal domi?nant inherited disorder characterized by early onset of colorectal cancer, predominance of proximal and multiple tumors, and microsatellite instability. In order to identify HNPCC, the international "Amsterdam criteria" have been used. Case report. The proband was a 40-year-old male who was admitted to hospital with a diagnosis of advanced rectal cancer. Left colectomy was carried out. A histopathologic diagnosis of poorly differentiated adenocarcinoma of clinical stage Dukes C was made. The family talking was done and it was revealed that the pro-band had five family members (one of first degree relative) with colorectal cancer, and two successive generations affected. All malignancy were diagnosed before 45 years of age. In one family member, metachronous transverse cancer was revealed 12 years after surgery for cecal adenocarcinoma. Discussion and conclusion. The main molecular cause for HNPCC is constitutional mutation in one of the mismatch repair (MMR) genes that regulate the excision of errors occurring during DNA replication. The most often are mutations of MLHI and MSH2 genes, and microsatellite instability is present in about 90-95% HNPCC. In this report, we present a case of an HNPCC patient who met the Amsterdam criteria for Lynch syndrome I. Family members that fulfill the Amsterdam criteria should be investigated for mutation in MMR genes. The genetic tests are not routinely available, so colonoscopic screening of all asymptomatic family members older than 25 has been recommended.

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