{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:20:19Z","timestamp":1781907619024,"version":"3.54.5"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Qatar University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Lynch syndrome (LS) is the most common cause of hereditary colorectal cancers (CRC) and is associated with an increased risk for ovarian and endometrial cancers. There is lack of knowledge on the epidemiology of LS in the non-Caucasian populations especially in Qatar. The aim of this retrospective study is to explore the prevalence of LS in a selected high-risk cohort in the State of Qatar in addition to investigating the frequency and genotype-phenotype correlation associated with mismatch repair genes pathogenic variants. Retrospective review of medical records of 31 individuals with LS, 20 affected with colorectal cancer and 11 unaffected with family history of cancers, referred from January 2017 until August 2020. The prevalence of LS among affected and unaffected patients is 22% (20\/92) and 2.2% respectively. Among affected individuals, MLH1 and MSH2 genes were highly frequent while for unaffected individuals, a recurrent PMS2 pathogenic variant was reported in several related individuals suggesting a tribal effect. This study highlights the epidemiology of LS in high-risk cohort in Qatar which helps to provide recommendations on genetic testing, and personalize surveillance and management programs<\/jats:p>","DOI":"10.3390\/genes13112176","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T03:04:20Z","timestamp":1669086260000},"page":"2176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prevalence and Genotype-Phenotype Correlation of Lynch Syndrome in a Selected High-Risk Cohort from Qatar\u2019s Population"],"prefix":"10.3390","volume":"13","author":[{"given":"Mariem","family":"Sidenna","sequence":"first","affiliation":[{"name":"Department of Adult and Pediatric Medical Genetics, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Department of Cancer Genetics, Medical Oncology, National Center of Cancer Care and Research, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houssein","family":"Khodjet-El-khil","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajar","family":"Al Mulla","sequence":"additional","affiliation":[{"name":"Department of Adult and Pediatric Medical Genetics, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Department of Cancer Genetics, Medical Oncology, National Center of Cancer Care and Research, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mashael","family":"Al-Shafai","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hind Hassan","family":"Habish","sequence":"additional","affiliation":[{"name":"Department of Cancer Genetics, Medical Oncology, National Center of Cancer Care and Research, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"AL-Sulaiman","sequence":"additional","affiliation":[{"name":"Department of Adult and Pediatric Medical Genetics, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Department of Cancer Genetics, Medical Oncology, National Center of Cancer Care and Research, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salha Bujassoum","family":"Al-Bader","sequence":"additional","affiliation":[{"name":"Department of Cancer Genetics, Medical Oncology, National Center of Cancer Care and Research, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nature07943","article-title":"The cancer genome","volume":"458","author":"Stratton","year":"2009","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1001\/jama.2012.13088","article-title":"Identification of Lynch syndrome among patients with colorectal cancer","volume":"308","author":"Moreira","year":"2012","journal-title":"JAMA"},{"key":"ref_3","first-page":"2167","article-title":"The proportion of endometrial cancers associated with Lynch syndrome: A systematic review of the literature and meta-analysis","volume":"21","author":"Ryan","year":"2019","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"909","DOI":"10.3892\/mco.2014.397","article-title":"Features of ovarian cancer in Lynch syndrome (Review)","volume":"2","author":"Nakamura","year":"2014","journal-title":"Mol. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1136\/gutjnl-2012-304356","article-title":"Revised guidelines for the clinical management of Lynch syndrome (HNPCC): Recommendations by a group of European experts","volume":"62","author":"Vasen","year":"2013","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1897-4287-11-9","article-title":"Germline deletions in the EPCAM gene as a cause of Lynch syndrome\u2014Literature review","volume":"11","author":"Tutlewska","year":"2013","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1007\/s00384-013-1685-x","article-title":"Genotype-phenotype correlation in MMR mutation-positive families with Lynch syndrome","volume":"28","author":"Infante","year":"2013","journal-title":"Int. J. Color. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0016-5085(99)70510-X","article-title":"New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC","volume":"116","author":"Vasen","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/jmg.37.9.641","article-title":"Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1","volume":"37","author":"Syngal","year":"2000","journal-title":"J. Med. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5783","DOI":"10.1200\/JCO.2008.17.5950","article-title":"Feasibility of screening for Lynch syndrome among patients with colorectal cancer","volume":"26","author":"Hampel","year":"2008","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13629","DOI":"10.1073\/pnas.93.24.13629","article-title":"hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6","volume":"93","author":"Acharya","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1086\/337944","article-title":"Molecular and clinical characteristics of MSH6 variants: An analysis of 25 index carriers of a germline variant","volume":"70","author":"Berends","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0002-9440(10)63841-2","article-title":"Conventional and tissue microarray immunohistochemical expression analysis of mismatch repair in hereditary colorectal tumors","volume":"162","author":"Hendriks","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1016\/S0002-9440(10)63062-3","article-title":"Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: Parallel pathways of tumorigenesis","volume":"159","author":"Young","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Valle, L., Gruber, S.B., and Capell\u00e1, G. (2018). The International Mismatch Repair Consortium. Hereditary Colorectal Cancer: Genetic Basis and Clinical Implications, Springer International Publishing.","DOI":"10.1007\/978-3-319-74259-5"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1200\/JCO.2005.03.7333","article-title":"Genotype-phenotype comparison of German MLH1 and MSH2 mutation carriers clinically affected with Lynch syndrome: A report by the German HNPCC Consortium","volume":"24","author":"Goecke","year":"2006","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1897-4287-8-5","article-title":"MSH6 and PMS2 mutation positive Australian Lynch syndrome families: Novel mutations, cancer risk and age of diagnosis of colorectal cancer","volume":"8","author":"McPhillips","year":"2010","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/sj.ejhg.5201584","article-title":"Phenotypic and genotypic heterogeneity in the Lynch syndrome: Diagnostic, surveillance and management implications","volume":"14","author":"Lynch","year":"2006","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s12032-014-0223-1","article-title":"Clinicopathological and genetic features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC)","volume":"31","author":"Liu","year":"2014","journal-title":"Med. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/mgg3.474","article-title":"Clinical genetics and genomic medicine in Qatar","volume":"6","author":"Shahbeck","year":"2018","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/mgg3.534","article-title":"Cancer genetics program: Follow-up on clinical genetics and genomic medicine in Qatar","volume":"6","author":"Alsulaiman","year":"2018","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13053-019-0128-2","article-title":"Prevalence and spectrum of MLH1, MSH2, and MSH6 pathogenic germline variants in Pakistani colorectal cancer patients","volume":"17","author":"Rashid","year":"2019","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10689-017-0015-9","article-title":"Screening for Lynch syndrome in young Saudi colorectal cancer patients using microsatellite instability testing and next generation sequencing","volume":"17","author":"Alqahtani","year":"2018","journal-title":"Fam. Cancer"},{"key":"ref_24","first-page":"98","article-title":"Prevalence of hereditary nonpolyposis colorectal cancer in patients with colorectal cancer in Iran: A systematic review","volume":"3","author":"Esmaeilzadeh","year":"2016","journal-title":"Rev. Clin. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1001\/jamaoncol.2016.5194","article-title":"Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients with Early-Onset Colorectal Cancer","volume":"3","author":"Pearlman","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1136\/jmg.2007.048991","article-title":"Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer)","volume":"44","author":"Vasen","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1002\/cncr.29288","article-title":"Prevalence of Lynch syndrome in a Middle Eastern population with colorectal cancer","volume":"121","author":"Siraj","year":"2015","journal-title":"Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1056\/NEJMoa043146","article-title":"Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer)","volume":"352","author":"Hampel","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/BF02054116","article-title":"Frequency of hereditary nonpolyposis colorectal cancer","volume":"38","author":"Mecklin","year":"1995","journal-title":"Dis. Colon Rectum"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1136\/gutjnl-2011-300041","article-title":"Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer","volume":"61","author":"Guarinos","year":"2012","journal-title":"Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1136\/jmg.2010.077677","article-title":"Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers","volume":"47","author":"Sjursen","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_32","first-page":"15","article-title":"Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: Findings from the Prospective Lynch Syndrome Database","volume":"22","author":"Sampson","year":"2020","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ramchander, N.C., Ryan, N.A., Crosbie, E.J., and Evans, D.G. (2017). Homozygous germ-line mutation of the PMS2 mismatch repair gene: A unique case report of constitutional mismatch repair deficiency (CMMRD). BMC Med. Genet., 18.","DOI":"10.1186\/s12881-017-0391-x"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/cr.2007.115","article-title":"Mechanisms and functions of DNA mismatch repair","volume":"18","author":"Li","year":"2008","journal-title":"Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/ajg.2017.105","article-title":"Recommendations on Surveillance and Management of Biallelic Mismatch Repair Deficiency (BMMRD) Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer","volume":"112","author":"Durno","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1053\/j.gastro.2005.10.052","article-title":"Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome)","volume":"130","author":"Hendriks","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1053\/j.gastro.2015.05.006","article-title":"Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome","volume":"149","author":"Yurgelun","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10689-012-9591-x","article-title":"EPCAM deletion carriers constitute a unique subgroup of Lynch syndrome patients","volume":"12","author":"Ligtenberg","year":"2013","journal-title":"Fam. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/humu.23688","article-title":"EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome","volume":"40","author":"Pathak","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_40","first-page":"35","article-title":"Impact of consanguinity on cancer in a highly endogamous population","volume":"10","author":"Bener","year":"2009","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1634\/theoncologist.2019-0552","article-title":"Molecular Analyses of Left- and Right-Sided Tumors in Adolescents and Young Adults with Colorectal Cancer","volume":"25","author":"Salem","year":"2020","journal-title":"Oncologist"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/S1525-1578(10)60549-1","article-title":"Analysis of hMLH1 and hMSH2 gene dosage alterations in hereditary nonpolyposis colorectal cancer patients by novel methods","volume":"7","author":"Baudhuin","year":"2005","journal-title":"J. Mol. Diagn. JMD"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.2147\/CMAR.S248069","article-title":"Evaluation of Concordance Between Deficient Mismatch Repair and Microsatellite Instability Testing and Their Association with Clinicopathological Features in Colorectal Cancer","volume":"12","author":"Bai","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_44","unstructured":"NCCN (2021, February 18). Genetic\/Familial High Risk Assessment: Colorectal. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/genetics_colon.pdf."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:23:12Z","timestamp":1760145792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/11\/2176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,21]]},"references-count":44,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["genes13112176"],"URL":"https:\/\/doi.org\/10.3390\/genes13112176","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,21]]}}}