Early Screening and Risk Stratification of Lynch Syndrome-Associated Multiple Cancers: From Colorectal Cancer to Endometrial Cancer and Pancreatic Cancer
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v6i2.4047
Abstract
Lynch syndrome (LS), an autosomal dominant hereditary disorder, represents the most prevalent form of hereditary colorectal cancer. LS patients are prone to developing multiple types of cancer, and the risk of different cancers caused by different pathogenic genes varies. The characteristic feature of LS is early damage to colorectal tumors, which mainly depends on the type of pathogenic mutation in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2, and EPCAM). Although colorectal cancer (CRC) is the most common cancer type in LS families, patients also have an increased lifetime risk of other types of tumors such as endometrial cancer (EC) and pancreatic cancer (PC). This study reviews the early diagnosis of multi-cancer in LS patients, explores approaches to reduce missed diagnoses and high mortality rates in LS-associated hereditary multi-cancers, and for the first time proposed the concept of multicancer screening, which encompasses several closely related and common cancers in LS syndromes and guided clinicians in early identifying and diagnosing at-risk individuals.
Keywords
lynch syndrome, hereditary colorectal cancer, endometrial cancer, pancreatic cancer, early screening, mismatch repair deficiency.
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[3]Roudko V, Cimen Bozkus C, Greenbaum B et al. Lynch Syndrome and MSI-H Cancers: From Mechanisms to "Off-The-Shelf" Cancer Vaccines. Front Immunol 2021, 12:757804.
[4]Xiao B, Luo J, Xie E et al. Comparisons of screening strategies for identifying Lynch syndrome among patients with MLH1-deficient colorectal cancer. Eur J Hum Genet 2020, 28(11):1555-1562.
[5]Biller LH, Creedon SA, Klehm M et al. Lynch Syndrome-Associated Cancers Beyond Colorectal Cancer. Gastrointest Endosc Clin N Am 2022, 32(1):75-93.
[6]Blaker H, Haupt S, Morak M et al. Age-dependent performance of BRAF mutation testing in Lynch syndrome diagnostics. Int J Cancer 2020, 147(10):2801-2810.
[7]Gao XH, Zhang W, Liu LJ et al. Comprehensive application of various screening strategies of Lynch syndrome. Zhonghua Wei Chang Wai Ke Za Zhi 2019, 22(7):684-688.
[8]Jass JR, Biden KG, Cummings MC et al. Characterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways. J Clin Pathol 1999, 52(6):455-460.
[9]Luo H, Zhao Q, Wei W et al. Circulating tumor DNA methylation profiles enable early diagnosis, prognosis prediction, and screening for colorectal cancer. Sci Transl Med 2020, 12(524)
[10]Parker WM, Hennig K, Burton-Chase AM. For Women, Lynch Syndrome Is About More than Colon Cancer. Cancer Prev Res (Phila) 2019, 12(12):831-836.
[11]Bujanda L, Herreros-Villanueva M. Pancreatic Cancer in Lynch Syndrome Patients. J Cancer 2017, 8(18):3667-3674.
[12]Gilani M, Intenzo CM, Bar-Ad V et al. Pancreatic Cancer in Lynch Syndrome: A Case Report. Case Rep Pancreat Cancer 2016, 2(1):36-39.
[13]Matsubayashi H, Takaori K, Morizane C et al. Familial pancreatic cancer: Concept, management and issues. World J Gastroenterol 2017, 23(6):935-948.
[14]Hofseth LJ, Hebert JR, Chanda A et al. Early-onset colorectal cancer: initial clues and current views. Nat Rev Gastroenterol Hepatol 2020, 17(6):352-364.
[15]Bray F, Laversanne M, Sung H et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024, 74(3):229-263.
[16]Seppala TT, Latchford A, Negoi I et al. European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender. Br J Surg 2021, 108(5):484-498.
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[18]Raut JR, Guan Z, Schrotz-King P et al. Fecal DNA methylation markers for detecting stages of colorectal cancer and its precursors: a systematic review. Clin Epigenetics 2020, 12(1):122.
[19]Xie Y, Li P, Sun D et al. DNA Methylation-Based Testing in Peripheral Blood Mononuclear Cells Enables Accurate and Early Detection of Colorectal Cancer. Cancer Res 2023, 83(21):3636-3649.
[20]Niu F, Wen J, Fu X et al. Stool DNA Test of Methylated Syndecan-2 for the Early Detection of Colorectal Neoplasia. Cancer Epidemiol Biomarkers Prev 2017, 26(9):1411-1419.
[21]Walsh MD, Cummings MC, Buchanan DD et al. Molecular, pathologic, and clinical features of early-onset endometrial cancer: identifying presumptive Lynch syndrome patients. Clin Cancer Res 2008, 14(6):1692-1700.
[22]Provenzale D, Gupta S, Ahnen DJ et al. Genetic/Familial High-Risk Assessment: Colorectal Version 1.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2016, 14(8):1010-1030.
[23]Lancaster JM, Powell CB, Kauff ND et al. Society of Gynecologic Oncologists Education Committee statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol 2007, 107(2):159-162.
[24]Weiss JM, Gupta S, Burke CA et al. NCCN Guidelines(R) Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021. J Natl Compr Canc Netw 2021, 19(10):1122-1132.
[25]Stelloo E, Jansen AML, Osse EM et al. Practical guidance for mismatch repair-deficiency testing in endometrial cancer. Ann Oncol 2017, 28(1):96-102.
[26]Wang C, Kuang W, Zeng J et al. A retrospective study of consistency between immunohistochemistry and polymerase chain reaction of microsatellite instability in endometrial cancer. PeerJ 2023, 11:e15920.
[27]Waleleng BJ, Adiwinata R, Wenas NT et al. Screening of pancreatic cancer: Target population, optimal timing and how? Ann Med Surg (Lond) 2022, 84:104814.
[28]Hendifar AE, Larson BK, Rojansky R et al. Pancreatic cancer 'mismatch' in Lynch syndrome. BMJ Open Gastroenterol 2019, 6(1):e000274.
[29]Welinsky S, Lucas AL. Familial Pancreatic Cancer and the Future of Directed Screening. Gut Liver 2017, 11(6):761-770.
[30]Costas-Chavarri A, Nandakumar G, Temin S et al. Treatment of Patients With Early-Stage Colorectal Cancer: ASCO Resource-Stratified Guideline. J Glob Oncol 2019, 5:1-19.
[31]Nguyen THH, Lu YT, Le VH et al. Clinical validation of a ctDNA-Based Assay for Multi-Cancer Detection: An Interim Report from a Vietnamese Longitudinal Prospective Cohort Study of 2795 Participants. Cancer Invest 2023:1-17.
[32]Soltesz B, Urbancsek R, Pos O et al. Quantification of peripheral whole blood, cell-free plasma and exosome encapsulated mitochondrial DNA copy numbers in patients with atrial fibrillation. J Biotechnol 2019, 299:66-71.
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