Published in:
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
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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.