scholarly journals Spectrum and Frequency of Tumors, Cancer Risk and Survival in Chilean Families with Lynch Syndrome: Experience of the Implementation of a Registry

2020 ◽  
Vol 9 (6) ◽  
pp. 1861
Author(s):  
Karin Álvarez ◽  
Paulina Orellana ◽  
Marjorie De la Fuente ◽  
Tamara Canales ◽  
Eliana Pinto ◽  
...  
Keyword(s):  
At Risk ◽  
Latin America ◽  
Cancer Risk ◽  
Lynch Syndrome ◽  
Genetic Counselling ◽  
Cumulative Incidence ◽  
Cancer Risks ◽  
Diagnostic Practice ◽  
Common Cancer ◽  
Extracolonic Cancers

Lynch syndrome (LS) is associated with the highest risk of colorectal (CRC) and several extracolonic cancers. In our effort to characterize LS families from Latin America, this study aimed to describe the spectrum of neoplasms and cancer risk by gender, age and gene, and survival in 34 Chilean LS families. Of them, 59% harbored path_MLH1, 23% path_MSH2, 12% path_PMS2 and 6% path_EPCAM variants. A total of 866 individuals at risk were identified, of which 213 (24.6%) developed 308 neoplasms. In males, CRC was the most common cancer (72.6%), while females showed a greater frequency of extracolonic cancers (58.4%), including uterus and breast (p < 0.0001). The cumulative incidence of extracolonic cancers was higher in females than males (p = 0.001). Path_MLH1 variants are significantly more associated with the development of CRC than extracolonic tumors (59.5% vs. 40.5%) when compared to path_MSH2 (47.5% vs. 52.5%) variants (p = 0.05018). The cumulative incidence of CRC was higher in path_MLH1/path_MSH2 carriers compared to path_PMS2 carriers (p = 0.03). In addition, path_MSH2 carriers showed higher risk of extracolonic tumors (p = 0.002). In conclusion, this study provides a snapshot of the LS profile from Chile and the current LS-associated diagnostic practice and output in Chile. Categorizing cancer risks associated with each population is relevant in the genetic counselling of LS patients.

scholarly journals Impact of genetic testing on endometrial cancer risk-reducing practices in women at risk for Lynch syndrome

2012 ◽  
Vol 127 (3) ◽  
pp. 544-551 ◽  
Author(s):  
Matthew B. Yurgelun ◽  
Rowena Mercado ◽  
Margery Rosenblatt ◽  
Monica Dandapani ◽  
Wendy Kohlmann ◽  
...  
Keyword(s):  
At Risk ◽  
Endometrial Cancer ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Lynch Syndrome ◽  
Endometrial Cancer Risk ◽  
Risk Reducing

scholarly journals Germline genomic patterns are associated with cancer risk, oncogenic pathways and clinical outcomes

2019 ◽  
Author(s):  
Xiaowen Feng ◽  
Xue Xu ◽  
Derek Li ◽  
Qinghua Cui ◽  
Edwin Wang
Keyword(s):  
Cancer Risk ◽  
Clinical Outcomes ◽  
Genome Instability ◽  
Cancer Risks ◽  
Systematic Analysis ◽  
Common Cancer ◽  
Oncogenic Pathways ◽  
Cancer Types ◽  
Genomic Patterns ◽  
Present Gene

SummaryGermline genetic polymorphism is prevalent and inheritable. So far mutations of a handful of genes have been associated with cancer risks. For example, women who harbor BRCA1/2 germline mutations have a 70% of cumulative breast cancer risk; individuals with congenital germline APC mutations have nearly 100% of cumulative colon cancer by the age of fifty. At present, gene-centered cancer predisposition knowledge explains only a small fraction of the inheritable cancer cases. Here we conducted a systematic analysis of the germline genomes of cancer patients (n=9,712) representing 22 common cancer types along with non-cancer individuals (n=16,670), and showed that seven germline genomic patterns, or significantly repeatedly occurring sequential mutation profiles, could be associated with both carcinogenesis processes and cancer clinical outcomes. One of the genomic patterns was significantly enriched in the germline genomes of patients who smoked than in those of non-smoker patients of 13 common cancer types, suggesting that the germline genomic pattern was likely to confer an elevated carcinogenesis sensitivity to tobacco smoke. Several patterns were also associated with somatic mutations of key oncogenic genes and somatic-mutational signatures which are associated with higher genome instability in tumors. Furthermore, subgroups defined by the germline genomic patterns were significantly associated with distinct oncogenic pathways, tumor histological subtypes and prognosis in 12 common cancer types, suggesting that germline genomic patterns enable to inform treatment and clinical outcomes. These results demonstrated that genetic cancer risk and clinical outcomes could be encoded in germline genomes in the form of not only mutated genes, but also specific germline genomic patterns, which provided a novel perspective for further investigation.

Perceptions of Cancer Risks and Predictors of Colon and Endometrial Cancer Screening in Women Undergoing Genetic Testing for Lynch Syndrome

2008 ◽  
Vol 26 (6) ◽  
pp. 948-954 ◽  
Author(s):  
Donald W. Hadley ◽  
Jean F. Jenkins ◽  
Seth M. Steinberg ◽  
David Liewehr ◽  
Stephanie Moller ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endometrial Cancer ◽  
Genetic Counseling ◽  
Genetic Testing ◽  
Cancer Screening ◽  
Lynch Syndrome ◽  
Test Results ◽  
Cancer Risks ◽  
Before And After ◽  
Extracolonic Cancers

Purpose Lynch syndrome poses multiple cancer risks, yet attention has focused on screening for colorectal cancer. Estimated risks for endometrial cancer equal risks for colorectal cancer. This study (1) evaluated women's perceived risks for cancers, (2) compared endometrial cancer screening and colonoscopy, and (3) identified predictors of screening before and after genetic testing. Patients and Methods Sixty-five adult women at 50% risk for carrying a cancer-predisposing mutation, without a history of endometrial cancer or hysterectomy, participated in genetic counseling and received unequivocal genetic test results for Lynch syndrome. Participants completed questionnaires before and after receipt of genetic results. Results Pretest, perceived risks for colon cancer were significantly higher than for extracolonic cancers (P < .0001). Use of colonoscopy was significantly higher (P = .006) than endometrial cancer screening. Post-test, carriers demonstrated a significant (P < .0001) increase in their perceived risk for extracolonic cancers and increased both colonoscopy (P = .79) and endometrial cancer screening (P = .11). Mutation status, age, perceived likelihood of carrying a mutation, and communication of test results to their physician independently predicted cancer screening at follow-up. Conclusion Women in families with Lynch syndrome are less aware of their risks for extracolonic cancers and undergo endometrial cancer screening significantly less often than colonoscopy before genetic counseling. Given the significantly increased risks for endometrial and ovarian cancers and the mortality associated with ovarian cancer, additional efforts to inform families of cancer risks and screening recommendations seem prudent. Physicians play a critical role in ensuring appropriate cancer screening in women with Lynch syndrome.

Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling

2017 ◽  
Vol 147 (2) ◽  
pp. 381-387 ◽  
Author(s):  
Sharon E. Johnatty ◽  
Yen Y. Tan ◽  
Daniel D. Buchanan ◽  
Michael Bowman ◽  
Rhiannon J. Walters ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Lynch Syndrome ◽  
Genetic Counselling ◽  
Endometrial Cancer Risk ◽  
Family History Of Cancer ◽  
History Of ◽  
History Of Cancer

scholarly journals Comparison of variant detection rate in genes between two cohorts of Czech living patients versus victims of sudden cardiac death with clinical / post mortem diagnosis of non-ischemic cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Borisincova ◽  
P Votypka ◽  
K Rucklova ◽  
A Pilin ◽  
M Kulvajtova ◽  
...  
Keyword(s):  
At Risk ◽  
Czech Republic ◽  
Primary Prevention ◽  
Sudden Cardiac Death ◽  
Genetic Counselling ◽  
Cardiac Death ◽  
Detection Rate ◽  
Funding Source ◽  
Post Mortem ◽  
Custom Made

Abstract Introduction Hereditary cardiomyopathy is associated with an increased risk of ventricular arrhythmia and sudden cardiac death (SCD). Genetic stratification substantiates risk assessment and enables the primary prevention of SCD in relatives at risk. We have analyzed the genetic aetiology of SCD in a representative Czech cohort with post mortem diagnosis of various forms of cardiomyopathy and compared it to living cases with these cardiac disorders. Patients and methods Between 2018 and 2019, altogether 47 victims of SCD with post mortem diagnosis of hypertrophic- (HCM; 18/47), arrhythmogenic- (ACM; 19/47) and dilated cardiomyopathy (DCM; 10/47) were identified. Concurrently, genetic testing was performed in 114 living patients (HCM 54/114, ACM 22/114, DCM 38/114). Genetic counselling and cardiologic examination had been carried out in first-degree relatives in all patients/SCD victims. Massively parallel sequencing (MiSeq platform; Illumina.com) was utilized for a custom-made panel comprising 100 candidate genes (Sophia Genetics, Switzerland). The presence of pathogenic variants was validated by Sanger DNA sequencing and through family segregation analyses. Results The causative detection rate (according to ACMG.net classes 4 or 5) in SCD victims with DCM was 60% (6/10) and in living patients with DCM 47.4% (18/38). Variants in TTN, RBM20, DES and FLNC (mainly truncating variants) prevailed in both groups. The detection rate in ACM was 5% (1/19 in SCN5A gene) in SCD victims and 31.8% (7/22) in living patients. Interestingly, the most prevalent mutated gene PKP2 in living patients was not detected in SCD victims. The detection rate in SCD victims with post mortem diagnosis of HCM was 16% (3/18) and in living patients 35% (19/54). The most prevalent gene was MYBPC3 in both groups, while PRKAG2 was detected in one SCD victim and in one living case who survived cardiac arrest. Conclusion Post-mortem genetic analysis in DCM yields a high detection rate and allows potentially effective primary prevention of SCD in relatives at risk. In contrast, the molecular autopsy of HCM and ACM renders a much lower yield which is below the mutation detection rate in living phenotype positive individuals. The results help to improve the genetic counselling in affected families in Czech Republic. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic

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