Analysis of a RECQL splicing mutation, c.1667_1667+3delAGTA, in breast cancer patients and controls from Central Europe

N Bogdanova, K Pfeifer, P Schürmann, N Antonenkova… - Familial Cancer, 2017 - Springer
N Bogdanova, K Pfeifer, P Schürmann, N Antonenkova, W Siggelkow, H Christiansen…
Familial Cancer, 2017Springer
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 …
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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