The lynch syndrome - a tip of an iceberg: a review of articles
DOI:
https://doi.org/10.18203/2320-6012.ijrms20250715Keywords:
Lynch syndrome, HNPCC, MSI, MMR, NGSAbstract
Lynch syndrome priorly was known as hereditary non-polyposis colorectal cancer (HNPCC), is an autosomal dominant hereditary disorder due to mutation in a mismatch repair (MMR) gene. Individuals with HNPCC are at increased risk for synchronous and metachronous colorectal cancer (CRC). Most common hereditary colorectal carcinoma syndrome (accounts for 2-5% of all colorectal carcinomas) along with 80% of patients develop colorectal carcinoma and also increased risk of endometrial carcinoma (60%), ovarian carcinoma (10-15%) and other cancers including gastric, ovarian, small bowel, urothelial (ureter, renal pelvis, and bladder), prostate, biliary tract, pancreatic, brain (glioblastoma), cutaneous sebaceous neoplasms. Most colorectal cancers are sporadic, but inherited syndromes cause 5% to 10% of cases. Patients with Lynch syndrome tend to develop carcinomas at an earlier age than the general population (average age: 44 years old). The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers. Molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. This article provides a framework for understanding the etiology of Lynch syndrome, including how to diagnose patients effectively, differentiate somatic from germline causes and how to monitor based on molecular presentation.
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Jass JR. Hereditary Non-Polyposis Colorectal Cancer: the rise and fall of a confusing term. World J Gastroenterol. 2006;12(31):4943-50. DOI: https://doi.org/10.3748/wjg.v12.i31.4943
Watson P, Riley B. The tumor spectrum in the Lynch syndrome. Fam Cancer. 2005;4(3):245-8. DOI: https://doi.org/10.1007/s10689-004-7994-z
Sehgal R, Sheahan K, O’Connell PR, Hanly AM, Martin ST, Winter DC. Centre for Colorectal Disease, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. Available at: https://www.stvincents.ie /research-and-education/our-research-groups/centre-colorectal-disease/. Accessed on 28 December 2024.
Lim A, Rao P, Matin SF. Lynch syndrome and urologic malignancies: a contemporary review. Curr Opin Urol. 2019;29(4):357-63. DOI: https://doi.org/10.1097/MOU.0000000000000639
Shih AR, Kradin RL. Malignant mesothelioma in Lynch syndrome: A report of two cases and a review of the literature. Am J Ind Med. 2019;62(5):448-52. DOI: https://doi.org/10.1002/ajim.22968
Kaur RJ, Pichurin PN, Hines JM, Singh RJ, Grebe SK, Bancos I. Adrenal Cortical Carcinoma Associated With Lynch Syndrome: A Case Report and Review of Literature. J Endocr Soc. 2019;3(4):784-90. DOI: https://doi.org/10.1210/js.2019-00050
Dominguez-Valentin M, Sampson JR, Seppälä TT, Ten Broeke SW, Plazzer JP, Nakken S, et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet Med. 2020;22(1):15-25.
Hendriks YM, Jagmohan-Changur S, van der Klift HM, Morreau H, van Puijenbroek M, Tops C, et al. Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome). Gastroenterology. 2006;130(2):312-22. DOI: https://doi.org/10.1053/j.gastro.2005.10.052
Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005;352(18):1851-60. DOI: https://doi.org/10.1056/NEJMoa043146
Neesham D. Ovarian Cancer Screening, Aust Fam Physician. 2007;36:126-8.
Lu KH. Hereditary Gynecologic Cancers: risk, prevention & management. Clinical relevence of hereditary endometrial cancer. 1st edition. Informer Healthcare; New York, NY. 2008;15-28. DOI: https://doi.org/10.3109/9781420052886-3
Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999;81(2):214-8. DOI: https://doi.org/10.1002/(SICI)1097-0215(19990412)81:2<214::AID-IJC8>3.3.CO;2-C
Parker WH, Broder MS, Liu Z, Shoupe D, Farquhar C, Berek JS. Ovarian conservation at the time of hysterectomy for benign disease. Obstet Gynecol. 2005;106(2):219-26. DOI: https://doi.org/10.1097/01.AOG.0000167394.38215.56
Yurgelun MB, Hampel H. Recent Advances in Lynch Syndrome: Diagnosis, Treatment, and Cancer Prevention. Am Soc Clin Oncol Educ Book. 2018;38:101-9.
NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Colorectal, Version 3. 2017. Available at: http://www.nccn.org/ professionals/ physician_gls/pdf/ genetics_colon.pdf Accessed on 27 December 2024.
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology. ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223-62. DOI: https://doi.org/10.1038/ajg.2014.435
Järvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomäki P, et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. 2000;118(5):829-34. DOI: https://doi.org/10.1016/S0016-5085(00)70168-5
Møller P, Seppälä T, Bernstein I, Holinski-Feder E, Sala P, Evans DG, et al; Mallorca Group (http://mallorca-group.eu). Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2017;66(3):464-72. DOI: https://doi.org/10.1136/gutjnl-2015-309675
Ahadova A, von Knebel Doeberitz M, Bläker H, Kloor M. CTNNB1-mutant colorectal carcinomas with immediate invasive growth: a model of interval cancers in Lynch syndrome. Fam Cancer. 2016;15(4):579-86. DOI: https://doi.org/10.1007/s10689-016-9899-z
Balmaña J, Balaguer F, Cervantes A, Arnold D; ESMO Guidelines Working Group. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2013;24(6):vi73-80. DOI: https://doi.org/10.1093/annonc/mdt209
Giardiello FM, Allen JI, Axilbund JE. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US multi -society task force on colorectal cancer. Gastroenterology. 2014;147:502-26. DOI: https://doi.org/10.1053/j.gastro.2014.04.001
Evans DG, Ingham SL. Reduced life expectancy seen in hereditary diseases which predispose to early-onset tumors. Appl Clin Genet. 2013;6:53-61. DOI: https://doi.org/10.2147/TACG.S35605
Dominguez-Valentin M, Sampson JR, Seppälä TT, Ten Broeke SW, Plazzer JP, Nakken S, et al. Cancer risks by gene, age, and gender in 6350carriers of pathogenic mismatch repair variants: findings from the Prospective LynchSyndrome Database. Genet Med. 2020;22(1):15-25. DOI: https://doi.org/10.1038/s41436-019-0716-6
Ryan S, Jenkins MA, Win AK. Risk of prostate cancer in Lynch syndrome: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014;23(3):437-49. DOI: https://doi.org/10.1158/1055-9965.EPI-13-1165
Joost P, Therkildsen C, Dominguez-Valentin M, Jönsson M, Nilbert M. Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations. Urology. 2015;86(6):1212-7. DOI: https://doi.org/10.1016/j.urology.2015.08.018
Bhattacharya P, Leslie SW, McHugh TW. Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer). In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2024.
Meyer LA, Broaddus RR, Lu KH. Departments of Gynecologic Oncology (LAM, KHL) and Pathology (RRB) at The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Available at: https://faculty.mdanderson.org/profiles/larissa_meyer.html. Accessed on 27 December 2024.
Yurgelun MB, Hampel H. Recent Advances in Lynch Syndrome: Diagnosis, Treatment, and Cancer Prevention. Am Soc Clin Oncol Educ Book. 2018;38:101-9. DOI: https://doi.org/10.1200/EDBK_208341
Domingo E, Laiho P, Ollikainen M, Pinto M, Wang L, French AJ, et al. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet. 2004;41(9):664-8. DOI: https://doi.org/10.1136/jmg.2004.020651
Nakamura K, Banno K, Yanokura M, Iida M, Adachi M, Masuda K, et al. Features of ovarian cancer in Lynch syndrome (Review). Mol Clin Oncol. 2014;2(6):909-16. DOI: https://doi.org/10.3892/mco.2014.397
Lindor NM, Petersen GM, Hadley DW, Kinney AY, Miesfeldt S, Lu KH, et al. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA. 2006;296(12):1507-17. DOI: https://doi.org/10.1001/jama.296.12.1507
Vasen HF, Möslein G, Alonso A, Bernstein I, Bertario L, Blanco I, et al. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet. 2007;44(6):353-62. DOI: https://doi.org/10.1136/jmg.2007.048991
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