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Open Access 01-12-2019 | Breast Cancer | Epidemiology

Inherited variants in XRCC2 and the risk of breast cancer

Authors: Wojciech Kluźniak, Dominika Wokołorczyk, Bogna Rusak, Tomasz Huzarski, Jacek Gronwald, Klaudia Stempa, Helena Rudnicka, Aniruddh Kashyap, Tadeusz Dębniak, Anna Jakubowska, Marcin Lener, Marek Szwiec, Joanna Tomiczek-Szwiec, Joanna Jarkiewicz-Tretyn, Magdalena Cechowska, Paweł Domagała, Agata Szymiczek, Maryam Bagherzadeh, Jan Lubiński, Steven A. Narod, Mohammad R. Akbari, Cezary Cybulski, the Polish Hereditary Breast Cancer Consortium

Published in: Breast Cancer Research and Treatment | Issue 3/2019

Abstract

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

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

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

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.

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Title: Inherited variants in XRCC2 and the risk of breast cancer
Authors: Wojciech Kluźniak
Dominika Wokołorczyk
Bogna Rusak
Tomasz Huzarski
Jacek Gronwald
Klaudia Stempa
Helena Rudnicka
Aniruddh Kashyap
Tadeusz Dębniak
Anna Jakubowska
Marcin Lener
Marek Szwiec
Joanna Tomiczek-Szwiec
Joanna Jarkiewicz-Tretyn
Magdalena Cechowska
Paweł Domagała
Agata Szymiczek
Maryam Bagherzadeh
Jan Lubiński
Steven A. Narod
Mohammad R. Akbari
Cezary Cybulski
the Polish Hereditary Breast Cancer Consortium
Publication date: 01-12-2019
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05415-5

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