Abstract
RECQL is a DNA helicase required for genomic stability. Two studies have recently identified RECQL as a novel breast cancer susceptibility gene. The most common RECQL mutation, the 4 bp-deletion c.1667_1667+3delAGTA, was five-fold enriched in Polish breast cancer patients, but the exact magnitude of the risk is uncertain. We investigated two hospital-based breast cancer case–control series from Belarus and Germany, respectively, comprising a total of 2596 breast cancer patients and 2132 healthy females. The mutation was found in 9 cases and 6 controls, with an adjusted Odds Ratio 1.23 (95% CI 0.44–3.47; p = 0.69) in the combined analysis. Among the cases, heterozygosity for c.1667_1667+3delAGTA was linked with estrogen-receptor positive breast cancer. There was no significant difference in age at diagnosis between carriers and non-carriers, and only one of the carriers reported a first-degree family history. Meta-analysis with the initial study from Poland suggests an about two-fold increase in risk for this mutation (OR 2.51; 95% CI 1.13–5.57, p = 0.02). Altogether, the data indicate that RECQL* c.1667_1667+3delAGTA is not a high-risk mutation for breast cancer though it could represent a moderate-risk breast cancer susceptibility allele. Further studies will be required to determine the clinical significance of testing for this RECQL mutation.
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Acknowledgements
We thank the patients and healthy volunteers for their participation and the many clinicians at hospitals in Belarus and Hannover for their support of this work. The Hannover laboratory was supported by the Rudolf Bartling Foundation, the Lower Saxonian Cancer Society and the Claudia von Schilling Foundation for Breast Cancer Research.
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Natalia Bogdanova and Katja Pfeifer are joint first authors.
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Bogdanova, N., Pfeifer, K., Schürmann, P. et al. Analysis of a RECQL splicing mutation, c.1667_1667+3delAGTA, in breast cancer patients and controls from Central Europe. Familial Cancer 16, 181–186 (2017). https://doi.org/10.1007/s10689-016-9944-y
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DOI: https://doi.org/10.1007/s10689-016-9944-y