Inherited variants in XRCC2 and the risk of breast cancer.
Breast cancer
Hereditary
Mutation
XRCC2
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
09
08
2019
accepted:
19
08
2019
pubmed:
30
8
2019
medline:
21
3
2020
entrez:
30
8
2019
Statut:
ppublish
Résumé
XRCC2 participates in homologous recombination and in DNA repair. XRCC2 has been reported to be a breast cancer susceptibility gene and is now included in several breast cancer susceptibility gene panels. We sequenced XRCC2 in 617 Polish women with familial breast cancer and found a founder mutation. We then genotyped 12,617 women with breast cancer and 4599 controls for the XRCC2 founder mutation. We identified a recurrent truncating mutation of XRCC2 (c.96delT, p.Phe32fs) in 3 of 617 patients with familial breast cancer who were sequenced. The c.96delT mutation was then detected in 29 of 12,617 unselected breast cancer cases (0.23%) compared to 11 of 4599 cancer-free women (0.24%) (OR = 0.96; 95% CI 0.48-1.93). The mutation frequency in 1988 women with familial breast cancer was 0.2% (OR = 0.84, 95% CI 0.27-2.65). Breast cancers in XRCC2 mutation carriers and non-carriers were similar with respect to age of diagnosis and clinical characteristics. Loss of the wild-type XRCC2 allele was observed only in one of the eight breast cancers from patients who carried the XRCC2 mutation. No cancer type was more common in first- or second-degree relatives of XRCC2 mutation carriers than in relatives of the non-carriers. XRCC2 c.96delT is a protein-truncating founder variant in Poland. There is no evidence that this mutation predisposes to breast cancer (and other cancers). It is premature to consider XRCC2 as a breast cancer-predisposing gene.
Sections du résumé
BACKGROUND
BACKGROUND
XRCC2 participates in homologous recombination and in DNA repair. XRCC2 has been reported to be a breast cancer susceptibility gene and is now included in several breast cancer susceptibility gene panels.
METHODS
METHODS
We sequenced XRCC2 in 617 Polish women with familial breast cancer and found a founder mutation. We then genotyped 12,617 women with breast cancer and 4599 controls for the XRCC2 founder mutation.
RESULTS
RESULTS
We identified a recurrent truncating mutation of XRCC2 (c.96delT, p.Phe32fs) in 3 of 617 patients with familial breast cancer who were sequenced. The c.96delT mutation was then detected in 29 of 12,617 unselected breast cancer cases (0.23%) compared to 11 of 4599 cancer-free women (0.24%) (OR = 0.96; 95% CI 0.48-1.93). The mutation frequency in 1988 women with familial breast cancer was 0.2% (OR = 0.84, 95% CI 0.27-2.65). Breast cancers in XRCC2 mutation carriers and non-carriers were similar with respect to age of diagnosis and clinical characteristics. Loss of the wild-type XRCC2 allele was observed only in one of the eight breast cancers from patients who carried the XRCC2 mutation. No cancer type was more common in first- or second-degree relatives of XRCC2 mutation carriers than in relatives of the non-carriers.
CONCLUSION
CONCLUSIONS
XRCC2 c.96delT is a protein-truncating founder variant in Poland. There is no evidence that this mutation predisposes to breast cancer (and other cancers). It is premature to consider XRCC2 as a breast cancer-predisposing gene.
Identifiants
pubmed: 31463769
doi: 10.1007/s10549-019-05415-5
pii: 10.1007/s10549-019-05415-5
pmc: PMC6817746
doi:
Substances chimiques
DNA-Binding Proteins
0
XRCC2 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
657-663Subventions
Organisme : Narodowe Centrum Nauki
ID : 2015/17/B/NZ5/02543
Investigateurs
M Bębenek
(M)
D Godlewski
(D)
S Gozdecka-Grodecka
(S)
S Goźdź
(S)
O Haus
(O)
H Janiszewska
(H)
M Jasiówka
(M)
E Kilar
(E)
R Kordek
(R)
B Kozak-Klonowska
(B)
G Książkiewicz
(G)
A Mackiewicz
(A)
E Marczak
(E)
J Mituś
(J)
Z Morawiec
(Z)
S Niepsuj
(S)
R Sibilski
(R)
M Siołek
(M)
J Sir
(J)
D Surdyka
(D)
A Synowiec
(A)
C Szczylik
(C)
R Uciński
(R)
B Waśko
(B)
R Wiśniowski
(R)
T Byrski
(T)
B Górski
(B)
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