Analysis of a RECQL splicing mutation, c.1667_1667+3delAGTA, in breast cancer patients and controls from Central Europe.
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.
Clinics of Obstetrics and Gynaecology, Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.|Clinics of Radiation Oncology, Hannover Medical School, Hannover, Germany.
Natalia
N
Bogdanova
Clinics of Obstetrics and Gynaecology, Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Katja
K
Pfeifer
Clinics of Obstetrics and Gynaecology, Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Peter
P
Schürmann
N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
Natalia
N
Antonenkova
Hospital DIAKOVERE Henriettenstift, Hannover, Germany.
Wulf
W
Siggelkow
Clinics of Radiation Oncology, Hannover Medical School, Hannover, Germany.
Hans
H
Christiansen
Clinics of Obstetrics and Gynaecology, Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Peter
P
Hillemanns
Clinics of Obstetrics and Gynaecology, Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
Tjoung-Won
TW
Park-Simon
Clinics of Obstetrics and Gynaecology, Gynaecology Research Unit, Hannover Medical School, Hannover, Germany. doerk.thilo@mh-hannover.de.
Thilo
T
Dörk
D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005858:Germany; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011044:Poland; D012326:RNA Splicing / Q000235:genetics; D053484:RecQ Helicases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism; D002094:Republic of Belarus; D018570:Risk Assessment
D011960:Receptors, Estrogen; C506725:RECQL protein, human; D053484:RecQ Helicases
Breast carcinoma; Chromosome breakage syndrome; DNA double-strand break repair; Founder mutation; Genetic susceptibility