title: High prevalence and breast cancer predisposing role of the BLM c.1642 C>T (Q548X) mutation in Russia.
abstract: The BLM gene belongs to the RecQ helicase family and has been implicated in the maintenance of genomic stability. Its homozygous germline inactivation causes Bloom syndrome, a severe genetic disorder characterized by growth retardation, impaired fertility and highly elevated cancer risk. We hypothesized that BLM is a candidate gene for breast cancer (BC) predisposition. Sequencing of its entire coding region in 95 genetically enriched Russian BC patients identified two heterozygous carriers of the c.1642 C>T (Q548X) mutation. The extended study revealed this allele in 17/1,498 (1.1%) BC cases vs. 2/1,093 (0.2%) healthy women (p = 0.004). There was a suggestion that BLM mutations were more common in patients reporting first-degree family history of BC (6/251 (2.4%) vs. 11/1,247 (0.9%), p = 0.05), early-onset cases (12/762 (1.6%) vs. 5/736 (0.7%), p = 0.14) and women with bilateral appearance of the disease (2/122 (1.6%) vs. 15/1376 (1.1%), p = 0.64). None of the BLM-associated BC exhibited somatic loss of heterozygosity at the BLM gene locus. This study demonstrates that BLM Q548X allele is recurrent in Slavic subjects and may be associated with BC risk.
authors.affiliation: N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Sokolenko
authors.forename: Aglaya G
authors.initials: AG
authors.lastname: Iyevleva
authors.forename: Elena V
authors.initials: EV
authors.lastname: Preobrazhenskaya
authors.forename: Nathalia V
authors.initials: NV
authors.lastname: Mitiushkina
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Abysheva
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Suspitsin
authors.forename: Ekatherina Sh
authors.initials: ESh
authors.lastname: Kuligina
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Gorodnova
authors.forename: Werner
authors.initials: W
authors.lastname: Pfeifer
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Togo
authors.forename: Elena A
authors.initials: EA
authors.lastname: Turkevich
authors.forename: Alexandr O
authors.initials: AO
authors.lastname: Ivantsov
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Voskresenskiy
authors.forename: Georgy D
authors.initials: GD
authors.lastname: Dolmatov
authors.forename: Elena M
authors.initials: EM
authors.lastname: Bit-Sava
authors.forename: Dmitry E
authors.initials: DE
authors.lastname: Matsko
authors.forename: Vladimir F
authors.initials: VF
authors.lastname: Semiglazov
authors.forename: Iduna
authors.initials: I
authors.lastname: Fichtner
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Larionov
authors.forename: Sergey G
authors.initials: SG
authors.lastname: Kuznetsov
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053484:RecQ Helicases / Q000235:genetics*; D012307:Risk Factors; D012426:Russia; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: C097151:Bloom syndrome protein; D053484:RecQ Helicases