Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts

Vasen, Hans F. A.; Blanco, Ignacio; Aktán-Collán, Katja; Gopie, Jessica P.; Alonso, Ángel; Aretz, Stefan; Bernstein, Inge; Bertario, Lucio; Burn, John; Capellà, Gabriel; Colas, Chrystelle; Engel, Christoph; Frayling, Ian Martin; Genuardi, Maurizio; Heinimann, Karl; Hes, Frederik J.; Hodgson, Shirley; Karagiannis, John A.; Lalloo, Fiona; Lindblom, Annika; Mecklin∥, Jukka–Pekka; Møller, Pål; Myrhøj, T; Nagengast, Fokko M.; Parc, Yann; Leòn, Maurizio Ponz de; Renkonen–Sinisalo, Laura; Sampson, Julian R.; Stormorken, Astrid; Sijmons, Rolf H.; Tejpar, Sabine; Thomas, Huw; Rahner, Nils; Wijnen, Juul T.; Järvinen, Heikki; Möslein, Gabriela

doi:10.1136/gutjnl-2012-304356

Cited by 633 publications

(614 citation statements)

References 123 publications

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“…In addition to cancer surveillance, carriers of MMR germline mutations can benefit from cancer preventive measures including prophylactic surgeries and preimplantation genetic diagnosis, which will prevent further transmission of the germline mutations to future generations. 13,37,38 Although LS has been extensively characterized in a Western population and the current study is not novel, to the best of our knowledge, the true incidence of LS in Saudi Arabia has not been reported to date. The incidence of LS in all CRC cases in the current study was 0.9%, which is in agreement with incidences reported in earlier studies.…”

Section: Discussionmentioning

confidence: 88%

Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer

Siraj

Prabhakaran

Bavi

et al. 2015

Cancer

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BACKGROUND: Lynch syndrome (LS; hereditary nonpolyposis colorectal cancer) is a common cause of hereditary colorectal cancer (CRC). CRC is the most common cancer diagnosed among males in Saudi Arabia but to the authors' knowledge there is a lack of data regarding the prevalence of LS in patients with CRC. There currently are no clear guidelines for the selection criteria for these patients to screen for LS. METHODS: A comprehensive molecular characterization was performed in a cohort of 807 CRC cases by immunohistochemical and microsatellite analysis using polymerase chain reaction. BRAF mutation screening, high CpG island methylator phenotype, and analysis for germline mutations were performed in 425 CRC samples. These were all high microsatellite instability (MSI-H) samples (91 cases), all low MSI samples (143 cases), and selected cases from the microsatellite stable group (191 cases) that met revised Bethesda guidelines. RESULTS: Polymerase chain reaction identified 91 MSI-H cases (11.3%) and sequencing revealed mismatch repair germline mutations in 8 CRC cases only. Of the total of 807 CRC cases, these 8 cases (0.99%) were MSI-H, met the revised Bethesda guidelines, and did not harbor BRAF mutations. CONCLUSIONS: The results of the current study confirmed cases of LS in approximately 1.0% of CRC samples and reflects the efficacy of screening among MSI-H cases that lack BRAF mutations. This comprehensive study from Saudi Arabia will help in implementing a universal screening/reflex testing strategy in a clinical setting in Saudi Arabia and in conducting a national screening program that benefits both patients and their relatives. Cancer 2015;121:1762-71.

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Section: Discussionmentioning

confidence: 88%

Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer

Siraj

Prabhakaran

Bavi

et al. 2015

Cancer

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“…However, as current guidelines do not recommend a single age cutoff for EC-based LS screening, 1,54,57,58 further investigation would be needed to shed light on this.…”

Section: Discussionmentioning

confidence: 99%

Which Lynch syndrome screening programs could be implemented in the “real world”? A systematic review of economic evaluations

Marco

D’Andrea

Panić

et al. 2018

Genetics in Medicine

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Purpose: Lynch syndrome (LS) screening can significantly reduce cancer morbidity and mortality in mutation carriers. Our aim was to identify cost-effective LS screening programs that can be implemented in the "real world."Methods: We performed a systematic review of full economic evaluations of genetic screening for LS in different target populations; health outcomes were estimated in life-years gained or quality-adjusted life-years.Results: Overall, 20 studies were included in the systematic review. Based on the study populations, we identified six categories of LS screening program: colorectal cancer (CRC)-based, endometrial cancer-based, general population-based, LS family registry-based, cascade testing-based, and genetics clinic-based screening programs. We performed an in-depth analysis of CRC-based LS programs, classifying them into three additional subcategories: universal, age-targeted, and selective. In five studies, universal programs based on immunohistochemistry, either alone or in combination with the BRAF test, were cost-effective compared with no screening, while in two studies age-targeted programs with a cutoff of 70 years were cost-effective when compared with agetargeted programs with lower age thresholds.Conclusion: Universal or o70 years-age-targeted CRC-based LS screening programs are cost-effective and should be implemented in the "real world." Genet Med advance online publication 4 January 2018Key Words: colorectal cancer; cost-effectiveness; Lynch syndrome; screening program; systematic review INTRODUCTIONLynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC), accounting for about 3% of newly diagnosed cases, and results from a mutation in one of the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2). As LS is associated with an increased risk of colorectal, endometrial, and other cancers, it is important to identify both the probands and their family members. 1 In 2009, the Evaluation of Genomic Applications in Practice and Prevention Working Group recommended testing for LS in individuals with newly diagnosed CRC to reduce cancer morbidity and mortality in relatives. 2 The working group declared that there is a moderate certainty that this would provide moderate population benefit, but it did not recommend a specific genetic testing strategy among the several examined, nor did it deal with implementation issues. 2 Thereafter the US Department of Health and Human Services adopted the following as a Healthy People 2020 developmental objective: 3 "Increase the proportion of persons with newly diagnosed colorectal cancer who receive genetic testing to identify Lynch syndrome (or familial colorectal cancer syndromes)."Although genomic information has the potential to improve the delivery of patient-centered care through tailored preventive, diagnostic, and treatment strategies, there is a considerable gap between discoveries in genomics research and the translation of these findings into genetic services that benefit patients. 4,5 A previous study highl...

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“…Enrollment in specialised registries and attendance at familial, high-risk gastrointestinal cancer clinics can facilitate the long-term care of such patients Vasen et al, 2014). There is no role for prophylactic colectomy, but prophylactic hysterectomy and bilateral salpingo-oophorectomy should be considered in women who have completed childbearing or after age 40 years as it significantly reduces the risk of both endometrial and ovarian cancer (Schmeler et al, 2006;Vasen et al, 2013). Recommended surveillance includes: colonoscopy every 1-2 years starting at age 25 (or 5 years younger than the youngest affected family member if <30 years), 2 yearly upper endoscopy starting age 30 in families with gastric cancer or at high ethnic risk.…”

Section: Rev Ised Bethesda Guidelinesmentioning

confidence: 99%

“…Both MSI detection and IHC are highly sensitive methods for the identification of a defective MMR system and guide clinicians towards informative, cost-effective genetic testing. These patients benefit from increased surveillance Jarvinen et al, 1995), prophylactic aspirin (Burn et al, 2011) and more radical surgery, (Heneghan et al, 2015;Vasen et al, 2013) and may also require different approaches to adjuvant therapy Sinicrope and Yang, 2011). 2.…”

Section: Introductionmentioning

confidence: 99%

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Ryan

Sheahan

Creavin

et al. 2017

Critical Reviews in Oncology/Hematology

118

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Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts

Cited by 633 publications

References 123 publications

Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer

Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer

Which Lynch syndrome screening programs could be implemented in the “real world”? A systematic review of economic evaluations

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

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