scholarly journals Evaluation of Lynch syndrome modifier genes in 748 MMR mutation carriers

2011 ◽  
Vol 19 (8) ◽  
pp. 887-892 ◽  
Author(s):  
Solene Houlle ◽  
Françoise Charbonnier ◽  
Estelle Houivet ◽  
Julie Tinat ◽  
Marie-Pierre Buisine ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Modifier Genes ◽  
Mutation Carriers

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.

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.

Mutation carriers’ perspectives on Lynch syndrome

2013 ◽  
Vol 27 (02) ◽  
pp. 74-75
Author(s):  
Helle Vendel Petersen
Keyword(s):  
Lynch Syndrome ◽  
Mutation Carriers

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 Determinants of adherence to recommendations for cancer prevention among Lynch Syndrome mutation carriers: A qualitative exploration

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0178205 ◽  
Author(s):  
Annemiek Visser ◽  
Alina Vrieling ◽  
Laxsini Murugesu ◽  
Nicoline Hoogerbrugge ◽  
Ellen Kampman ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Cancer Prevention ◽  
Mutation Carriers ◽  
Qualitative Exploration

Causes of death of mutation carriers in Finnish Lynch syndrome families

2012 ◽  
Vol 11 (3) ◽  
pp. 467-471 ◽  
Author(s):  
Kirsi Pylvänäinen ◽  
Tuula Lehtinen ◽  
Ilmo Kellokumpu ◽  
Heikki Järvinen ◽  
Jukka-Pekka Mecklin
Keyword(s):  
Lynch Syndrome ◽  
Causes Of Death ◽  
Mutation Carriers

scholarly journals Lynch syndrome: the influence of environmental factors on extracolonic cancer risk in hMLH1 c.C1528T mutation carriers and their mutation-negative sisters

2010 ◽  
Vol 9 (3) ◽  
pp. 357-363 ◽  
Author(s):  
M. M. Blokhuis ◽  
G. E. Pietersen ◽  
P. A. Goldberg ◽  
U. Algar ◽  
L. Van der Merwe ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Cancer Risk ◽  
Lynch Syndrome ◽  
Extracolonic Cancer ◽  
Mutation Carriers

scholarly journals Contribution of Lynch syndrome to early onset malignancy in Ireland.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 586-586
Author(s):  
Alice Talbot ◽  
David James Gallagher
Keyword(s):  
Lynch Syndrome ◽  
Cancer Diagnosis ◽  
Early Onset ◽  
Cancer Genetics ◽  
Statistical Significance ◽  
Hereditary Cancer Syndrome ◽  
Carrier Status ◽  
Mutation Carriers ◽  
Significant Difference ◽  
First Diagnosis

586 Background: Lynch syndrome (LS) is an autosomal dominant hereditary cancer syndrome responsible for 2 -6% of hereditary colorectal cancers. LS is caused by germ-line mutations in mismatch repair genes (MMR): MLH1, MSH2, MSH6, PMS2 or EPCAM. This results in microsatellite instability, a phenotypic hallmark of LS-associated colorectal cancer. The aim of this study was to construct and analyse a database of Irish MMR mutation carriers. Methods: Records were from two of the three existing cancer genetics clinics in Ireland. Clinicopathological data of all probands (n=57) including names, dates of birth and death, carrier status and phenotype were recorded. Death certificates were used to confirm information regarding deceased mutation carriers. An ANOVA test was used to establish statistical significance of variations in age by gene. Length of survival based on stage was assessed using Kaplain Meier curves. Results: 345 affected individuals were identified. The most common cancers recorded were colorectal (53%), breast (12%) and endometrial (10%). 138 confirmed carriers were identified: 65 MLH1 (47%), 43 MSH2 (31%), 11 MSH6 (8%), 17 PMS2 (12%), and 2 EPCAM (1%). 22 patients have died since confirmation of Lynch Syndrome, 50% of whom died within 2.5 years of first diagnosis. All deceased carriers had at least one cancer diagnosis and 50% had developed multiple cancers. 59% of deaths were directly related to cancer. 7 of these patients had Stage 4 cancer at diagnosis. There was a significant difference in length of survival based on stage. (p=.048) Phenotype frequencies varied significantly by gene. (see table 1) Median age of first diagnosis of any cancer was 44.5 years (range 23-81). There was no difference in age at presentation by gene mutated. Conclusions: Under-diagnosis of LS misses a powerful preventive and therapeutic opportunity. LS causes early onset cancer diagnosis with substantial societal impact. A significant number of Lynch Syndrome cases have poor clinical outcomes. Genotype/Phenotype frequencies. [Table: see text]

scholarly journals Cancer spectrum in DNA mismatch repair gene mutation carriers: results from a hospital based Lynch syndrome registry

2012 ◽  
Vol 11 (3) ◽  
pp. 441-447 ◽  
Author(s):  
Mala Pande ◽  
Chongjuan Wei ◽  
Jinyun Chen ◽  
Christopher I. Amos ◽  
Patrick M. Lynch ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Gene Mutation ◽  
Dna Mismatch Repair ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Dna Mismatch ◽  
Mutation Carriers ◽  
Dna Mismatch Repair Gene
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