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Breast Cancer Res Treat (2012) 133:809811 DOI 10.1007/s10549-012-2049-x
LETTER TO THE EDITOR
Germline mutations 657del5 and 643C>T (R215W) in NBN are not likely to be associated with increased risk of breast cancer in Czech women
Martin Mateju Petra Kleiblova Zdenek Kleibl
Marketa Janatova Jana Soukupova
Ivana Ticha Jan Novotny Petr Pohlreich
Received: 20 March 2012 / Accepted: 21 March 2012 / Published online: 11 April 2012 Springer Science+Business Media, LLC. 2012
To the Editor,
The NBN (formerly NBS1) gene (OMIM*602667) is located on chromosome 8q21 and encodes a 754-amino acid protein known as nibrin. Nibrin is a component of the MRE11/RAD50/NBN (MRN) complex and is involved in the DNA double-strand break repair, telomere maintenance, and cell-cycle checkpoint control. Individuals homozygous for deleterious mutations in NBN develop an autosomal recessive disorder, Nijmegen breakage syndrome (NBS; #251260), characterized by microcephaly, growth retardation, immunodeciency, hypersensitivity to X-irradiation, and increased risk of lymphoid malignancies [1]. About 90 % of NBS patients carry the homozygous mutation 657del5 (c.657_661delACAAA) affecting exon 6 of the NBN gene that has been predominantly identied in Slavic populations [2, 3]. Another potentially deleterious NBN alteration, the missense substitution c.643C[T(p.R215W), is also located in exon 6 and has been described in two severely affected NBS siblings who were compound heterozygotes for the 657del5 and R215W
mutations [4]. Previous studies suggested that heterozygous carriers of the founder mutation 657del5 or R215W have an increased risk of breast cancer (BC) in several European populations [57]. However, the role of these mutations was not tested in other countries and the 657del5 mutation did not contribute signicantly to BC risk in the German population [7, 8]. No deleterious NBN mutations were identied in China [9].
Based on the results of our analysis, we would like to contribute to the debate on the role of the 657del5 and R215W mutations in BC susceptibility. The frequency of both NBN mutations was analyzed in 1,303 Czech patients (including 600 high-risk, hereditary and non-hereditary, BRCA1/2-negative breast/ovarian cancer patients [10], and 703 consecutive unselected BC patients) and in 915 control non-cancer individuals (Table 1) [11]. The DNA was isolated from blood samples by routine procedures. Screening for mutations affecting exon 6 and adjacent intronic regions of the NBN gene was performed by a high resolution...