Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications
- PMID: 19659756
- PMCID: PMC2846640
- DOI: 10.1111/j.1399-0004.2009.01230.x
Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications
Abstract
More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (approximately 30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC's proximal occurrence (70-80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40-60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10-25% of familial CRC.
Figures
Similar articles
-
Muir-Torre Syndrome and founder mismatch repair gene mutations: A long gone historical genetic challenge.Gene. 2016 Sep 10;589(2):127-32. doi: 10.1016/j.gene.2015.06.078. Epub 2015 Jul 2. Gene. 2016. PMID: 26143115 Review.
-
What the physician needs to know about Lynch syndrome: an update.Oncology (Williston Park). 2005 Apr;19(4):455-63; discussion 463-4, 466, 469. Oncology (Williston Park). 2005. PMID: 15938070 Review.
-
Clinical implications of advances in the molecular genetics of colorectal cancer.Tumori. 1995 May-Jun;81(3 Suppl):19-29. Tumori. 1995. PMID: 7571049
-
Lynch syndrome: genetics, natural history, genetic counseling, and prevention.J Clin Oncol. 2000 Nov 1;18(21 Suppl):19S-31S. J Clin Oncol. 2000. PMID: 11060321
-
Practical genetics of colorectal cancer.Chin Clin Oncol. 2013 Jun;2(2):12. doi: 10.3978/j.issn.2304-3865.2013.03.04. Chin Clin Oncol. 2013. PMID: 25841492
Cited by
-
Universal screening of colorectal tumors for lynch syndrome: a survey of patient experiences and opinions.Hered Cancer Clin Pract. 2024 Sep 5;22(1):18. doi: 10.1186/s13053-024-00290-8. Hered Cancer Clin Pract. 2024. PMID: 39238026 Free PMC article.
-
Glioma oncogenesis in the Constitutional mismatch repair deficiency (CMMRD) syndrome.Neurooncol Adv. 2024 Jul 11;6(1):vdae120. doi: 10.1093/noajnl/vdae120. eCollection 2024 Jan-Dec. Neurooncol Adv. 2024. PMID: 39233831 Free PMC article.
-
MSH6 germline mutations leading to Lynch syndrome-associated cholangiocarcinoma: a case report.Front Oncol. 2024 Aug 5;14:1414665. doi: 10.3389/fonc.2024.1414665. eCollection 2024. Front Oncol. 2024. PMID: 39161380 Free PMC article.
-
Genome-wide detection of somatic mosaicism at short tandem repeats.Bioinformatics. 2024 Aug 2;40(8):btae485. doi: 10.1093/bioinformatics/btae485. Bioinformatics. 2024. PMID: 39078205 Free PMC article.
-
Pathological Features of Colorectal Adenocarcinoma Patients Related to MLH1.Cell Mol Bioeng. 2024 Feb 20;17(2):153-164. doi: 10.1007/s12195-024-00797-z. eCollection 2024 Apr. Cell Mol Bioeng. 2024. PMID: 38737450
References
-
- International Agency for Research on Cancer. Globocan 2002. 2008. [accessed on: 25 November 2008.]. Available at: http://www-dep.iarc.fr/
-
- Bussey HJR. Familial polyposis coli: family studies, histopathology, differential diagnosis, and results of treatment. Baltimore, MD: Johns Hopkins University Press; 1975.
-
- Bülow S, Faurschou NT, Bülow C, et al. The incidence rate of familial adenomatous polyposis. Results from the Danish Polyposis Register. Int J Colorectal Dis. 1996;11:88–91. - PubMed
-
- Aaltonen L, Johns L, Järvinen H, et al. Explaining the familial colorectal cancer risk associated with mismatch repair (MMR)-deficient and MMR-stable tumors. Clin Cancer Res. 2007;13:356–361. - PubMed
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources