Details of Disease

Disease Name

Lynch syndrome

hereditary nonpolyposis colorectal cancer; HNPCC - hereditary nonpolyposis colon cancer; hereditary nonpolyposis colorectal neoplasm; hereditary defective mismatch repair syndrome; Hereditary colorectal endometrial cancer syndrome; Lynch syndrome; familial non-polyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2); Hereditary non-polyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2); hereditary non-polyposis colon cancer type 1; Hereditary nonpolyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2)

Definition

An autosomal dominant hereditary neoplastic syndrome characterized by the development of colorectal carcinoma and a high risk of developing endometrial carcinoma, gastric carcinoma, ovarian carcinoma, renal pelvis carcinoma, and small intestinal carcinoma. Patients often develop colorectal carcinomas at an early age (mean, 45 years). In the majority of the cases the lesions arise from the proximal colon. At the molecular level, high-frequency microsatellite instability is present.|Sometimes Lynch syndrome is also referred to as hereditary non-polyposis colorectal cancer (HNPCC), but the two conditions are subtly different. Lynch syndrome is classified by a mutation in mismatch repair genes. It is diagnosed by specific criteria known as the Amsterdam criteria.

Disease Hierarchy

DISPA49R: Hereditary nonpolyposis colon cancer

DIS3HIWD: Autosomal dominant disease

DIS3IW5F: Lynch syndrome

Disease Identifiers

MONDO ID

MONDO_0005835

MESH ID

D003123

UMLS CUI

C4552100

MedGen ID

1633554

Orphanet ID

144

SNOMED CT ID

716318002

General Information of Disease (ID: DIS3IW5F)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 16 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PMS1	TTX1ISF	Refuted	Autosomal dominant	[1]
FAP	TTGPQ0F	Limited	Genetic Variation	[2]
MUTYH	TTNB0ZK	Limited	Biomarker	[3]
ANXA10	TT0NL6U	Strong	Altered Expression	[4]
BRIP1	TTZV7LJ	Strong	Genetic Variation	[5]
CD44	TTWFBT7	Strong	Biomarker	[6]
EPCAM	TTZ8WH4	Strong	Genetic Variation	[7]
GJA8	TTJ7ATH	Strong	Biomarker	[8]
MAT2A	TTSMPXQ	Strong	Biomarker	[9]
PMS1	TTX1ISF	Strong	Genetic Variation	[10]
RNASEL	TT7V0K4	Strong	Genetic Variation	[11]
RNF43	TTD91BL	Strong	Genetic Variation	[12]
TGFBR2	TTZE3P7	Strong	Biomarker	[13]
EPCAM	TTZ8WH4	Definitive	Autosomal dominant	[1]
MLH1	TTISG27	Definitive	Autosomal dominant	[1]
MSH2	TTCAWRT	Definitive	Autosomal dominant	[1]
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⏷ Show the Full List of 16 DTT(s)

This Disease Is Related to 28 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
EXO1	OTI87RS5	Refuted	Autosomal dominant	[1]
PMS1	OTOGFMI6	Refuted	Autosomal dominant	[1]
MSH3	OTD3YPVL	Limited	Autosomal dominant	[1]
POLD1	OTWO4UCJ	Limited	Genetic Variation	[14]
POLE	OTFM3MMU	Limited	Genetic Variation	[15]
RAD51C	OTUD6SY5	Limited	Genetic Variation	[5]
RPS20	OTI8052R	Limited	Autosomal dominant	[1]
SEMA4A	OT8901H3	Disputed	Autosomal dominant	[1]
FAN1	OT1LM1HZ	Supportive	Autosomal dominant	[16]
AIP	OTDJ3OSV	Strong	Genetic Variation	[17]
APC	OTKV0TIK	Strong	Genetic Variation	[18]
ATAD1	OTJ02XFL	Strong	Genetic Variation	[19]
EMB	OT67E3Q1	Strong	Biomarker	[20]
HEPACAM	OT1MJ51D	Strong	Biomarker	[21]
ITGA9	OTHN1IKA	Strong	Genetic Variation	[22]
KAT2A	OTN0W2SW	Strong	Biomarker	[23]
LRRFIP2	OTU8GUMV	Strong	Genetic Variation	[24]
MAX	OTKZ0YKM	Strong	Biomarker	[23]
NHS	OTKE8QAT	Strong	Biomarker	[25]
NPTN	OTAQKSAU	Strong	Biomarker	[26]
PALB2	OT6DNDBG	Strong	Genetic Variation	[27]
PTPRG	OT9N2WOF	Strong	Posttranslational Modification	[28]
SEC63	OT1ICPMK	Strong	Biomarker	[29]
EPCAM	OTHBZK5X	Definitive	Autosomal dominant	[1]
MLH1	OTG5XDD8	Definitive	Autosomal dominant	[1]
MSH2	OT10H1AB	Definitive	Autosomal dominant	[1]
MSH6	OT46FP09	Definitive	Autosomal dominant	[1]
PMS2	OTNLWTMI	Definitive	Autosomal dominant	[1]
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⏷ Show the Full List of 28 DOT(s)

References

1	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2	Identification of Lynch syndrome risk variants in the Romanian population.J Cell Mol Med. 2018 Dec;22(12):6068-6076. doi: 10.1111/jcmm.13881. Epub 2018 Oct 16.
3	Multi-gene panel testing confirms phenotypic variability in MUTYH-Associated Polyposis.Fam Cancer. 2019 Apr;18(2):203-209. doi: 10.1007/s10689-018-00116-2.
4	Immunohistochemistry for annexin A10 can distinguish sporadic from Lynch syndrome-associated microsatellite-unstable colorectal carcinoma.Am J Surg Pathol. 2014 Apr;38(4):518-25. doi: 10.1097/PAS.0000000000000148.
5	Time to incorporate germline multigene panel testing into breast and ovarian cancer patient care.Breast Cancer Res Treat. 2016 Dec;160(3):393-410. doi: 10.1007/s10549-016-4003-9. Epub 2016 Oct 12.
6	Functional Genomic mRNA Profiling of Colorectal Adenomas: Identification and in vivo Validation of CD44 and Splice Variant CD44v6 as Molecular Imaging Targets.Theranostics. 2017 Jan 6;7(2):482-492. doi: 10.7150/thno.16816. eCollection 2017.
7	Toward a better definition of EPCAM deletions in Lynch Syndrome: Report of new variants in Italy and the associated molecular phenotype.Mol Genet Genomic Med. 2019 May;7(5):e587. doi: 10.1002/mgg3.587. Epub 2019 Mar 27.
8	A new strategy to screen MMR genes in Lynch Syndrome: HA-CAE, MLPA and RT-PCR.Eur J Cancer. 2009 May;45(8):1485-93. doi: 10.1016/j.ejca.2009.01.030. Epub 2009 Feb 26.
9	Universal Point of Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma.J Urol. 2018 Jan;199(1):60-65. doi: 10.1016/j.juro.2017.08.002. Epub 2017 Aug 7.
10	Primary multiple tumor with affection of the thyroid gland, uterus, urinary bladder, mammary gland and other organs.Pathol Res Pract. 2017 May;213(5):574-579. doi: 10.1016/j.prp.2017.01.003. Epub 2017 Jan 19.
11	The additive effect of p53 Arg72Pro and RNASEL Arg462Gln genotypes on age of disease onset in Lynch syndrome patients with pathogenic germline mutations in MSH2 or MLH1.Cancer Lett. 2007 Jul 8;252(1):55-64. doi: 10.1016/j.canlet.2006.12.006. Epub 2007 Jan 16.
12	RNF43 is mutated less frequently in Lynch Syndrome compared with sporadic microsatellite unstable colorectal cancers.Fam Cancer. 2018 Jan;17(1):63-69. doi: 10.1007/s10689-017-0003-0.
13	EGFR, SMAD7, and TGFBR2 Polymorphisms Are Associated with Colorectal Cancer in Patients with Lynch Syndrome.Anticancer Res. 2018 Oct;38(10):5983-5990. doi: 10.21873/anticanres.12946.
14	Frameshift mutational target gene analysis identifies similarities and differences in constitutional mismatch repair-deficiency and Lynch syndrome.Mol Carcinog. 2017 Jul;56(7):1753-1764. doi: 10.1002/mc.22632. Epub 2017 Mar 30.
15	Risk of colorectal cancer for carriers of a germ-line mutation in POLE or POLD1.Genet Med. 2018 Aug;20(8):890-895. doi: 10.1038/gim.2017.185. Epub 2017 Nov 9.
16	Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair. Gastroenterology. 2015 Sep;149(3):563-6. doi: 10.1053/j.gastro.2015.05.056. Epub 2015 Jun 5.
17	Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4101-5. doi: 10.1073/pnas.0700004104. Epub 2007 Feb 28.
18	Excluding Lynch syndrome in a female patient with metachronous DNA mismatch repair deficient colon- and ovarian cancer.Fam Cancer. 2018 Jul;17(3):415-420. doi: 10.1007/s10689-017-0055-1.
19	Genetic variation in genes for the xenobiotic-metabolizing enzymes CYP1A1, EPHX1, GSTM1, GSTT1, and GSTP1 and susceptibility to colorectal cancer in Lynch syndrome.Cancer Epidemiol Biomarkers Prev. 2008 Sep;17(9):2393-401. doi: 10.1158/1055-9965.EPI-08-0326.
20	Immunohistochemistry for mismatch repair protein deficiency in endometrioid endometrial carcinoma yields equivalent results when performed on endometrial biopsy/curettage or hysterectomy specimens.Gynecol Oncol. 2018 Jun;149(3):570-574. doi: 10.1016/j.ygyno.2018.04.005. Epub 2018 Apr 13.
21	Advances in the study of Lynch syndrome in China.World J Gastroenterol. 2015 Jun 14;21(22):6861-71. doi: 10.3748/wjg.v21.i22.6861.
22	An interstitial deletion at 3p21.3 results in the genetic fusion of MLH1 and ITGA9 in a Lynch syndrome family.Clin Cancer Res. 2009 Feb 1;15(3):762-9. doi: 10.1158/1078-0432.CCR-08-1908.
23	Mutation and association analyses of the candidate genes ESR1, ESR2, MAX, PCNA, and KAT2A in patients with unexplained MSH2-deficient tumors.Fam Cancer. 2012 Mar;11(1):19-26. doi: 10.1007/s10689-011-9489-z.
24	A novel exonic rearrangement affecting MLH1 and the contiguous LRRFIP2 is a founder mutation in Portuguese Lynch syndrome families.Genet Med. 2011 Oct;13(10):895-902. doi: 10.1097/GIM.0b013e31821dd525.
25	Cost-effectiveness analysis of reflex testing for Lynch syndrome in women with endometrial cancer in the UK setting.PLoS One. 2019 Aug 30;14(8):e0221419. doi: 10.1371/journal.pone.0221419. eCollection 2019.
26	Improving the uptake of predictive testing and colorectal screening in Lynch syndrome: a regional primary care survey.Clin Genet. 2015 Jun;87(6):517-24. doi: 10.1111/cge.12559. Epub 2015 Feb 4.
27	Metastatic Prostate Cancer: Effects of Genetic Testing on Care.Clin J Oncol Nurs. 2019 Feb 1;23(1):32-35. doi: 10.1188/19.CJON.32-35.
28	Tumour-specific methylation of PTPRG intron 1 locus in sporadic and Lynch syndrome colorectal cancer.Eur J Hum Genet. 2011 Mar;19(3):307-12. doi: 10.1038/ejhg.2010.187. Epub 2010 Dec 8.
29	Hepatocellular carcinoma as extracolonic manifestation of Lynch syndrome indicates SEC63 as potential target gene in hepatocarcinogenesis.Scand J Gastroenterol. 2013 Mar;48(3):344-51. doi: 10.3109/00365521.2012.752030.