Association of recurrent mutations in BRCA1, BRCA2, RAD51C, PALB2, and CHEK2 with the risk of borderline ovarian tumor.
BRCA1
BRCA2
Borderline ovarian tumor
CHEK2
Low-grade ovarian cancer
PALB2
RAD51C
Recurrent mutations
Journal
Hereditary cancer in clinical practice
ISSN: 1731-2302
Titre abrégé: Hered Cancer Clin Pract
Pays: Poland
ID NLM: 101231179
Informations de publication
Date de publication:
21 Mar 2022
21 Mar 2022
Historique:
received:
22
12
2021
accepted:
08
03
2022
entrez:
22
3
2022
pubmed:
23
3
2022
medline:
23
3
2022
Statut:
epublish
Résumé
There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs. The study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated. The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45-15.43, p=0.01). Results suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required.
Sections du résumé
BACKGROUND
BACKGROUND
There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs.
METHODS
METHODS
The study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated.
RESULTS
RESULTS
The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45-15.43, p=0.01).
CONCLUSIONS
CONCLUSIONS
Results suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required.
Identifiants
pubmed: 35313928
doi: 10.1186/s13053-022-00218-0
pii: 10.1186/s13053-022-00218-0
pmc: PMC8935754
doi:
Types de publication
Journal Article
Langues
eng
Pagination
11Subventions
Organisme : This research was funded by Minister of Science and Higher Education "Regional Initiative of Excellence" in years 2019-2022
ID : Grant No 002/RID/2018/19
Informations de copyright
© 2022. The Author(s).
Références
Oncologist. 2012;17(12):1515-33
pubmed: 23024155
Biochem Genet. 1993 Aug;31(7-8):321-8
pubmed: 8274138
Best Pract Res Clin Obstet Gynaecol. 2017 May;41:15-30
pubmed: 28277307
Diagn Pathol. 2012 Sep 20;7:124
pubmed: 22995373
Cancers (Basel). 2020 Apr 13;12(4):
pubmed: 32295079
Am J Obstet Gynecol. 2014 Dec;211(6):637.e1-6
pubmed: 24949545
Gynecol Oncol. 2005 Jun;97(3):780-3
pubmed: 15893369
Gynecol Oncol. 2002 Jul;86(1):34-7
pubmed: 12079297
Eur J Gynaecol Oncol. 2009;30(5):471-82
pubmed: 19899396
Mod Pathol. 2005 Feb;18 Suppl 2:S19-32
pubmed: 15761464
Acta Obstet Gynecol Scand. 2016 Apr;95(4):473-9
pubmed: 26714557
Taiwan J Obstet Gynecol. 2015 Aug;54(4):398-402
pubmed: 26384058
Am J Hum Genet. 2004 Dec;75(6):1131-5
pubmed: 15492928
Int J Cancer. 2003 Oct 10;106(6):942-5
pubmed: 12918074
Cancer. 2004 Mar 1;100(5):1045-52
pubmed: 14983501
Obstet Gynecol. 2012 Sep;120(3):612-8
pubmed: 22914471
Lancet Oncol. 2015 Jun;16(6):638-44
pubmed: 25959805
Histol Histopathol. 2006 Apr;21(4):341-7
pubmed: 16437378
N Engl J Med. 1997 Apr 17;336(16):1125-30
pubmed: 9099656
Int J Cancer. 2008 Oct 15;123(8):1897-901
pubmed: 18661518
J Med Genet. 2021 May;58(5):305-313
pubmed: 32546565
Best Pract Res Clin Obstet Gynaecol. 2012 Jun;26(3):325-36
pubmed: 22321906
Cancer Res. 2004 Apr 15;64(8):2677-9
pubmed: 15087378
Clin Genet. 2015 Mar;87(3):288-92
pubmed: 24528374
J Natl Cancer Inst. 1998 Jul 1;90(13):995-1000
pubmed: 9665148
Cancers (Basel). 2020 Aug 17;12(8):
pubmed: 32824581
Clin Cancer Res. 2005 Oct 15;11(20):7273-9
pubmed: 16243797
J Clin Oncol. 2015 Sep 10;33(26):2901-7
pubmed: 26261251
Eur J Cancer. 2006 Jan;42(2):149-58
pubmed: 16326097
Int J Gynecol Cancer. 2007 Sep-Oct;17(5):1143-7
pubmed: 17386038
Cancers (Basel). 2021 Feb 18;13(4):
pubmed: 33670479
Virchows Arch. 2017 Feb;470(2):125-142
pubmed: 28025670
Br J Cancer. 2004 Nov 15;91(10):1829-34
pubmed: 15477862
Int J Cancer. 2019 Dec 15;145(12):3311-3320
pubmed: 31173646
Gynecol Oncol. 2006 Sep;102(3):429-31
pubmed: 16828850
Int J Gynecol Cancer. 2013 Nov;23(9):1597-602
pubmed: 24172096
J Appl Genet. 2011 May;52(2):185-91
pubmed: 21120647
Am J Hum Genet. 2001 Mar;68(3):700-10
pubmed: 11179017
J Menopausal Med. 2014 Apr;20(1):14-20
pubmed: 25371887
J Natl Cancer Inst. 2015 Aug 27;107(11):
pubmed: 26315354