title: Nonsense mutation p.Q548X in BLM, the gene mutated in Bloom's syndrome, is associated with breast cancer in Slavic populations.
abstract: Bloom's syndrome is a rare autosomal recessive chromosomal instability disorder with a high incidence of various types of neoplasia, including breast cancer. Whether monoallelic BLM mutations predispose to breast cancer has been a long-standing question. A nonsense mutation, p.Q548X, has recently been associated with an increased risk for breast cancer in a Russian case-control study. In the present work, we have investigated the prevalence of this Slavic BLM founder mutation in a total of 3,188 breast cancer cases and 2,458 controls from Bashkortostan, Belarus, Ukraine, and Kazakhstan. The p.Q548X allele was most frequent in Russian patients (0.8 %) but was also prevalent in Byelorussian and Ukrainian patients (0.5 and 0.6 %, respectively), whereas it was absent in Altaic or other non-European subpopulations. In a combined analysis of our four case-control series, the p.Q548X mutation was significantly associated with breast cancer (Mantel-Haenszel OR 5.1, 95 % CI 1.2; 21.9, p = 0.03). A meta-analysis with the previous study from the St. Petersburg area corroborates the association (OR 5.7, 95 % CI 2.0; 15.9, p = 3.7 × 10(-4)). A meta-analysis for all published truncating mutations further supports the association of BLM with breast cancer, with an estimated two- to five-fold increase in risk (OR 3.3, 95 %CI 1.9; 5.6, p = 1.9 × 10(-5)). Altogether, these data indicate that BLM is not only a gene for Bloom's syndrome but also might represent a breast cancer susceptibility gene.
authors.affiliation: Institute of Biochemistry and Genetics, Ufa Science Center, Ufa, Russia.
authors.forename: Darya
authors.initials: D
authors.lastname: Prokofyeva
authors.forename: Natalia
authors.initials: N
authors.lastname: Bogdanova
authors.forename: Natalia
authors.initials: N
authors.lastname: Dubrowinskaja
authors.forename: Marina
authors.initials: M
authors.lastname: Bermisheva
authors.forename: Zalina
authors.initials: Z
authors.lastname: Takhirova
authors.forename: Natalia
authors.initials: N
authors.lastname: Antonenkova
authors.forename: Nurzhan
authors.initials: N
authors.lastname: Turmanov
authors.forename: Ihor
authors.initials: I
authors.lastname: Datsyuk
authors.forename: Shamil
authors.initials: S
authors.lastname: Gantsev
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
authors.forename: Tjoung-Won
authors.initials: TW
authors.lastname: Park-Simon
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.forename: Elza
authors.initials: E
authors.lastname: Khusnutdinova
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001486:Bashkiria; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018389:Codon, Nonsense; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007623:Kazakhstan; D008875:Middle Aged; D053484:RecQ Helicases / Q000235:genetics*; D002094:Republic of Belarus; D014455:Ukraine
chemical_list: D018389:Codon, Nonsense; C097151:Bloom syndrome protein; D053484:RecQ Helicases