Recent progress in Lynch syndrome and other familial colorectal cancer syndromes

Boland, Patrick M.; Yurgelun, Matthew B.; Boland, C. Richard

doi:10.3322/caac.21448

Cited by 136 publications

(122 citation statements)

References 160 publications

(297 reference statements)

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…However, NGS studies have reported that as much as ~18% of patients diagnosed with CRC < age of 50 years have pathogenic variants in genes that are not traditionally associated with CRC ( ATM , CHEK2 , BRCA1 , BRCA2 , CDKN2A and PALB2 ) . Notably, there is a need to determine whether these variants contribute to hereditary CRC risk via the combination of low‐ and moderate‐penetrance susceptibility alleles …”

Section: Genetic Profile For Hereditary Crc: Lynch Syndromementioning

confidence: 99%

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Vaccaro

López-Köstner

Adriana

et al. 2018

Intl Journal of Cancer

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%–80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.

show abstract

Section: Genetic Profile For Hereditary Crc: Lynch Syndromementioning

confidence: 99%

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Vaccaro

López-Köstner

Adriana

et al. 2018

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The guidelines from the American College of Medical Genetics and Genomics guide the process of sequence variant classification using criteria informed by expert opinion and empirical data [40]. The guidelines from the National Comprehensive Cancer Network for LS use modified Bethesda criteria that take into account young age of onset and tumor screening to address low penetrance of germline pathogenic variants [41]. …”

Section: Aim 1: Assessing the Challenges And Opportunities Of Implemementioning

confidence: 99%

“…Universal tumor testing is cost-effective and sensitive for LS screening in individuals with colorectal and endometrial cancers [42, 43]. Using clinical prediction models is also cost-effective for individuals with or without cancer [41]. …”

Section: Aim 1: Assessing the Challenges And Opportunities Of Implemementioning

confidence: 99%

Challenges and Opportunities for Cancer Predisposition Cascade Screening for Hereditary Breast and Ovarian Cancer and Lynch Syndrome in Switzerland: Findings from an International Workshop

Nikolaidis

Ming

Pedrazzani

et al. 2018

Public Health Genomics

View full text Add to dashboard Cite

Background: An international workshop on cancer predisposition cascade genetic screening for hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) took place in Switzerland, with leading researchers and clinicians in cascade screening and hereditary cancer from different disciplines. The purpose of the workshop was to enhance the implementation of cascade genetic screening in Switzerland. Participants discussed the challenges and opportunities associated with cascade screening for HBOC and LS in Switzerland (CASCADE study); family implications and the need for family-based interventions; the need to evaluate the cost-effectiveness of cascade genetic screening; and interprofessional collaboration needed to lead this initiative. Methods: The workshop aims were achieved through exchange of data and experiences from successful cascade screening programs in the Netherlands, Australia, and the state of Ohio, USA; Swiss-based studies and scientific experience that support cancer cascade screening in Switzerland; programs of research in psychosocial oncology and family-based studies; data from previous cost-effectiveness analyses of cascade genetic screening in the Netherlands and in Australia; and organizational experience from a large interprofessional collaborative. Scientific presentations were recorded and discussions were synthesized to present the workshop findings. Results: The key elements of successful implementation of cascade genetic screening are a supportive network of stakeholders and connection to complementary initiatives; sample size and recruitment of relatives; centralized organization of services; data-based cost-effectiveness analyses; transparent organization of the initiative; and continuous funding. Conclusions: This paper describes the processes and key findings of an international workshop on cancer predisposition cascade screening, which will guide the CASCADE study in Switzerland.

show abstract

“…The majority of cases in this subset are characterized by hypermethylation of the MLH1 promoter, which is also observed in approximately 15% of sporadic CRC cases [4,5]. Variants in the BRAF oncogene are able to distinguish LS from sporadic MMRde cient CRC; this has been demonstrated to be a powerful method for screening patients with LS [6,7]. A subset of patients with CRC, who manifest the MMR de ciency but have no identi ed germline variant in either MMR genes or the BRAF gene (absence of MLH1 methylation), have been de ned as having Lynchlike syndrome (LLS) [1,3,8].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-like and Lynch Syndromes

Liu

Guo

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background: In this study, we compared the molecular, clinical, and pathological characteristics, as well as pedigrees, between patients with Lynch-like syndrome (LLS) and confirmed Lynch syndrome (LS) to develop appropriate management strategies for patients with LLS and their affected family members. Methods: Between June 2008 and September 2018, 81 patients with LLS and 47 patients with LS who developed colorectal cancer (CRC) were enrolled in this study. Multigene panel testing included 139 genes and was performed for all patients. The variants identified in each group were described, and clinicopathological characteristics and pedigrees were compared between the two groups. Results: In the LLS group, a total of 52 variants were detected in 44 (54.3%) patients. Among the 52 variants, 17 were variants of unknown significance in mismatch repair genes, and the other most frequently mutated genes were MUYTH, POLE, BRCA2, and GJB2. The proportion of early-onset patients was significantly higher among the LS probands than among the LLS probands (74.5% and 53.1%, respectively; χ2 = 5.712, P = 0.017). On the other hand, the proportion of primary CRC developed in the rectum was higher in the LLS group than in the LS group (25.9% and 10.6%, respectively; χ2 = 2.358, P = 0.046). There were no significant differences in the occurrence of metachronous CRC (P = 0.632) and extra-CRC (P = 0.145) between the two groups. However, analysis of pedigrees showed that more patients developed CRC in the LS families (P = 0.013), whereas more patients with extra-CRC were observed in the LLS families (P = 0.045). A higher prevalence of male patients was observed in the LLS families (P = 0.036). Conclusions: LLS should be classified as a mixed entity, containing cases of true LS, other hereditary cancer syndromes, and sporadic CRC. The high risks of CRC and extra-CRC, found in our study, suggest that aggressive surgical management should be performed for LLS probands. In addition, we recommend a stringent surveillance protocol that should involve regular follow-ups of the intestine and other organs for probands and affected family members.

show abstract

Recent progress in Lynch syndrome and other familial colorectal cancer syndromes

Cited by 136 publications

References 160 publications

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America

Challenges and Opportunities for Cancer Predisposition Cascade Screening for Hereditary Breast and Ovarian Cancer and Lynch Syndrome in Switzerland: Findings from an International Workshop

Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-like and Lynch Syndromes

Contact Info

Product

Resources

About