A search for modifying genetic factors in CHEK2:c.1100delC breast cancer patients.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 07 2021
20 07 2021
Historique:
received:
18
04
2021
accepted:
28
06
2021
entrez:
21
7
2021
pubmed:
22
7
2021
medline:
16
11
2021
Statut:
epublish
Résumé
The risk of breast cancer associated with CHEK2:c.1100delC is 2-threefold but higher in carriers with a family history of breast cancer than without, suggesting that other genetic loci in combination with CHEK2:c.1100delC confer an increased risk in a polygenic model. Part of the excess familial risk has been associated with common low-penetrance variants. This study aimed to identify genetic loci that modify CHEK2:c.1100delC-associated breast cancer risk by searching for candidate risk alleles that are overrepresented in CHEK2:c.1100delC carriers with breast cancer compared with controls. We performed whole-exome sequencing in 28 breast cancer cases with germline CHEK2:c.1100delC, 28 familial breast cancer cases and 70 controls. Candidate alleles were selected for validation in larger cohorts. One recessive synonymous variant, rs16897117, was suggested, but no overrepresentation of homozygous CHEK2:c.1100delC carriers was found in the following validation. Furthermore, 11 non-synonymous candidate alleles were suggested for further testing, but no significant difference in allele frequency could be detected in the validation in CHEK2:c.1100delC cases compared with familial breast cancer, sporadic breast cancer and controls. With this method, we found no support for a CHEK2:c.1100delC-specific genetic modifier. Further studies of CHEK2:c.1100delC genetic modifiers are warranted to improve risk assessment in clinical practice.
Identifiants
pubmed: 34285278
doi: 10.1038/s41598-021-93926-x
pii: 10.1038/s41598-021-93926-x
pmc: PMC8292481
doi:
Substances chimiques
Checkpoint Kinase 2
EC 2.7.1.11
CHEK2 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14763Informations de copyright
© 2021. The Author(s).
Références
Nat Genet. 2010 Oct;42(10):885-92
pubmed: 20852631
Nat Genet. 2020 Jan;52(1):56-73
pubmed: 31911677
Nat Genet. 2013 Apr;45(4):371-84, 384e1-2
pubmed: 23535731
JAMA. 2014 Jan 1;311(1):90-92
pubmed: 24381969
Genet Med. 2017 May;19(5):599-603
pubmed: 27711073
Nat Genet. 2008 Jul;40(7):844-53
pubmed: 18511948
Nat Commun. 2016 Apr 27;7:11375
pubmed: 27117709
J Med Genet. 2008 Jul;45(7):425-31
pubmed: 18413374
Int J Cancer. 2005 Feb 10;113(4):575-80
pubmed: 15472904
Biomed Res Int. 2013;2013:747318
pubmed: 23586058
Genet Med. 2019 Aug;21(8):1708-1718
pubmed: 30643217
Eur J Cancer. 2013 May;49(8):1993-9
pubmed: 23415889
Nat Genet. 2010 Nov;42(11):969-72
pubmed: 20890277
Nat Genet. 2016 Apr;48(4):374-86
pubmed: 26928228
Oncogene. 2006 Sep 25;25(43):5898-905
pubmed: 16998504
Breast Cancer Res. 2014 Dec 31;16(6):3416
pubmed: 25919761
Am J Hum Genet. 2004 Jun;74(6):1175-82
pubmed: 15122511
J Clin Oncol. 2008 Feb 1;26(4):542-8
pubmed: 18172190
J Clin Oncol. 2012 Dec 10;30(35):4308-16
pubmed: 23109706
Nat Commun. 2016 Sep 07;7:12675
pubmed: 27601076
Am J Hum Genet. 2019 Jan 3;104(1):21-34
pubmed: 30554720
Nat Rev Mol Cell Biol. 2001 Dec;2(12):877-86
pubmed: 11733767
Hum Mol Genet. 2011 Aug 15;20(16):3304-21
pubmed: 21593217
Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):230-4
pubmed: 19124502
Cancer Res. 2010 Dec 1;70(23):9742-54
pubmed: 21118973
Nat Genet. 2008 Jan;40(1):17-22
pubmed: 18163131
J Natl Cancer Inst. 2000 Sep 20;92(18):1529-31
pubmed: 10995809
Nat Genet. 2020 Jun;52(6):572-581
pubmed: 32424353
Am J Hum Genet. 2008 Apr;82(4):937-48
pubmed: 18355772
Nature. 2017 Nov 2;551(7678):92-94
pubmed: 29059683
Br J Cancer. 2002 Jan 7;86(1):76-83
pubmed: 11857015
Am J Hum Genet. 2002 Aug;71(2):432-8
pubmed: 12094328
PLoS Genet. 2013;9(3):e1003212
pubmed: 23544013
PLoS Genet. 2013;9(3):e1003173
pubmed: 23544012