Details of Disease

Disease Name

Hereditary nonpolyposis colon cancer

HNPCC; Hereditary nonpolyposis colorectal cancer (HNPCC); familial nonpolyposis colon cancer; hereditary nonpolyposis colon cancer; hereditary nonpolyposis colorectal cancer; familial nonpolyposis colorectal cancer; colorectal cancer, hereditary nonpolyposis

Definition

Hereditary nonpolyposis colon cancer (HNPCC) is a cancer-predisposing condition characterized by the development of colorectal cancer not associated with colorectal polyposis, endometrial cancer, and various other cancers (such as malignant epithelial tumor of ovary, gastric, biliary tract, small bowel, and urinary tract cancer) that are frequently diagnosed at an early age.

Disease Hierarchy

DISZYIBJ: Familial colorectal cancer

DISGXLG5: Hereditary neoplastic syndrome

DISPA49R: Hereditary nonpolyposis colon cancer

Disease Identifiers

MONDO ID

MONDO_0018630

MESH ID

D003123

UMLS CUI

C1333990

MedGen ID

232602

Orphanet ID

443909

SNOMED CT ID

315058005

General Information of Disease (ID: DISPA49R)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 41 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
XRCC4	OT4SXOIZ	Limited	Autosomal dominant	[1]
CTNNA1	OTFC725Z	No Known	Autosomal dominant	[1]
BARD1	OTTC0Z9Y	Limited	Autosomal dominant	[1]
CDKN1B	OTNY5LLZ	Limited	Autosomal recessive	[1]
CHEK2	OT8ZPCNS	Limited	Autosomal dominant	[1]
EPHX1	OTBKWQER	Limited	Autosomal dominant	[1]
FAN1	OT1LM1HZ	Limited	Autosomal dominant	[1]
NFKBIZ	OTU728KS	Limited	Autosomal dominant	[1]
PALB2	OT6DNDBG	Limited	Autosomal dominant	[1]
POLD1	OTWO4UCJ	Limited	Genetic Variation	[24]
POLE	OTFM3MMU	Limited	Genetic Variation	[25]
PTPRJ	OT10OKOF	Limited	Autosomal dominant	[1]
RAD51C	OTUD6SY5	Limited	Genetic Variation	[2]
RPS20	OTI8052R	Limited	Autosomal dominant	[26]
SEMA4A	OT8901H3	Limited	Biomarker	[27]
SMARCA4	OT68WOPQ	Limited	Autosomal dominant	[1]
STN1	OT8UWRA3	Limited	Biomarker	[28]
ATM	OTQVOHLT	Moderate	Autosomal dominant	[1]
AIP	OTDJ3OSV	Strong	Genetic Variation	[29]
APBA1	OTUH9JPD	Strong	Biomarker	[30]
ARSI	OTIANNWW	Strong	Biomarker	[31]
ATAD1	OTJ02XFL	Strong	Genetic Variation	[32]
CDHR2	OTTHEUPO	Strong	Biomarker	[33]
CDHR5	OTTBWQMN	Strong	Biomarker	[33]
CISD3	OT0MM1MW	Strong	Posttranslational Modification	[30]
EMB	OT67E3Q1	Strong	Biomarker	[34]
HEPACAM	OT1MJ51D	Strong	Biomarker	[35]
ITGA9	OTHN1IKA	Strong	Genetic Variation	[36]
KAT2A	OTN0W2SW	Strong	Biomarker	[37]
LRRFIP2	OTU8GUMV	Strong	Genetic Variation	[38]
MAX	OTKZ0YKM	Strong	Biomarker	[37]
MYH14	OT1TZEJK	Strong	Genetic Variation	[39]
NDUFAB1	OTF906UR	Strong	Genetic Variation	[40]
NHS	OTKE8QAT	Strong	Biomarker	[41]
NPTN	OTAQKSAU	Strong	Biomarker	[42]
PRB1	OTV0SYMD	Strong	Biomarker	[43]
PTPRG	OT9N2WOF	Strong	Posttranslational Modification	[44]
REEP5	OTZU4TJI	Strong	Biomarker	[45]
SEC63	OT1ICPMK	Strong	Biomarker	[46]
SPEN	OT37A2MD	Strong	Posttranslational Modification	[30]
SPRR2A	OT62ZU6B	Strong	Genetic Variation	[47]
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⏷ Show the Full List of 41 DOT(s)

This Disease Is Related to 27 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BRIP1	TTZV7LJ	Limited	Genetic Variation	[2]
CDH1	TTLAWO6	Limited	Biomarker	[3]
CDKN1B	TTLGFVW	Limited	Autosomal recessive	[1]
CDKN1B	TTLGFVW	Limited	Biomarker	[4]
CHEK2	TT9ABMF	Limited	Autosomal dominant	[1]
CHEK2	TT9ABMF	Limited	Biomarker	[5]
EPCAM	TTZ8WH4	Limited	Genetic Variation	[6]
MUTYH	TTNB0ZK	Limited	Biomarker	[7]
PTPRJ	TTWMKXP	Limited	Autosomal dominant	[1]
PTPRJ	TTWMKXP	Limited	Biomarker	[8]
SMARCA4	TTVQEZS	Limited	Autosomal dominant	[1]
SMARCA4	TTVQEZS	Limited	Biomarker	[9]
ATM	TTKBM7V	Moderate	Autosomal dominant	[1]
ATM	TTKBM7V	moderate	Biomarker	[10]
ACVR2A	TTX2DRI	Strong	Biomarker	[11]
ANXA10	TT0NL6U	Strong	Altered Expression	[12]
ARSA	TTYQANR	Strong	Biomarker	[11]
CD44	TTWFBT7	Strong	Biomarker	[13]
FAP	TTGPQ0F	Strong	Biomarker	[14]
FBXO11	TT6G10V	Strong	CausalMutation	[15]
GJA8	TTJ7ATH	Strong	Biomarker	[16]
MAT2A	TTSMPXQ	Strong	Biomarker	[17]
PMS1	TTX1ISF	Strong	Genetic Variation	[18]
RNASEL	TT7V0K4	Strong	Genetic Variation	[19]
RNF43	TTD91BL	Strong	Genetic Variation	[20]
SPTBN1	TTS9BDA	Strong	Genetic Variation	[21]
TGFBR2	TTZE3P7	Strong	Biomarker	[22]
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⏷ Show the Full List of 27 DTT(s)

This Disease Is Related to 3 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
EPHX1	DELB4KP	Limited	Autosomal dominant	[1]
EPHX1	DELB4KP	Limited	Biomarker	[4]
BAAT	DERA3OF	Strong	Genetic Variation	[23]
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References

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18	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.
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20	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.
21	Genomic mapping of chromosomal region 2p15-p21 (D2S378-D2S391): integration of Genemap'98 within a framework of yeast and bacterial artificial chromosomes.Genomics. 1999 Nov 15;62(1):21-33. doi: 10.1006/geno.1999.5957.
22	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.
23	Microsatellite instability analysis in hereditary non-polyposis colon cancer using the Bethesda consensus panel of microsatellite markers in the absence of proband normal tissue.BMC Med Genet. 2006 Jan 20;7:5. doi: 10.1186/1471-2350-7-5.
24	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.
25	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.
26	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
27	Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis. Am J Hum Genet. 2016 Aug 4;99(2):337-51. doi: 10.1016/j.ajhg.2016.06.015. Epub 2016 Jul 28.
28	Detection of Tn, sialosyl-Tn and T antigens in hereditary nonpolyposis colorectal cancer.Virchows Arch. 1996 Dec;429(6):345-52. doi: 10.1007/BF00198438.
29	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.
30	Promoter hypermethylation frequency and BRAF mutations distinguish hereditary non-polyposis colon cancer from sporadic MSI-H colon cancer.Fam Cancer. 2004;3(2):101-7. doi: 10.1023/B:FAME.0000039861.30651.c8.
31	Automated, multiplex assay for high-frequency microsatellite instability in colorectal cancer.J Clin Oncol. 2003 Aug 15;21(16):3105-12. doi: 10.1200/JCO.2003.11.133.
32	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.
33	Loss of expression of -protocadherin and protocadherin-24 in sporadic and hereditary nonpolyposis colorectal cancers.Hum Pathol. 2019 Feb;84:299-308. doi: 10.1016/j.humpath.2018.09.019. Epub 2018 Oct 5.
34	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.
35	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.
36	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.
37	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.
38	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.
39	Smooth-muscle myosin mutations in hereditary non-polyposis colorectal cancer syndrome.Br J Cancer. 2008 Nov 18;99(10):1726-8. doi: 10.1038/sj.bjc.6604737. Epub 2008 Oct 21.
40	Frequent mutation of beta-catenin and APC genes in primary colorectal tumors from patients with hereditary nonpolyposis colorectal cancer.Cancer Res. 1999 Sep 15;59(18):4506-9.
41	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.
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43	Mutations of two PMS homologues in hereditary nonpolyposis colon cancer.Nature. 1994 Sep 1;371(6492):75-80. doi: 10.1038/371075a0.
44	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.
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