TY - JOUR
T1 - High prevalence and breast cancer predisposing role of the BLM c.1642 C>T (Q548X) mutation in Russia
AU - Sokolenko, Anna P
AU - Iyevleva, Aglaya G
AU - Preobrazhenskaya, Elena V
AU - Mitiushkina, Nathalia V
AU - Abysheva, Svetlana N
AU - Suspitsin, Evgeny N
AU - Kuligina, Ekatherina Sh
AU - Gorodnova, Tatiana V
AU - Pfeifer, Werner
AU - Togo, Alexandr V
AU - Turkevich, Elena A
AU - Ivantsov, Alexandr O
AU - Voskresenskiy, Dmitry V
AU - Dolmatov, Georgy D
AU - Bit-Sava, Elena M
AU - Matsko, Dmitry E
AU - Semiglazov, Vladimir F
AU - Fichtner, Iduna
AU - Larionov, Alexey A
AU - Kuznetsov, Sergey G
AU - Antoniou, Antonis C
AU - Imyanitov, Evgeny N
N1 - Copyright © 2011 UICC.
PY - 2012/6/15
Y1 - 2012/6/15
N2 - 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.
AB - 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.
U2 - 10.1002/ijc.26342
DO - 10.1002/ijc.26342
M3 - Article
C2 - 21815139
VL - 130
SP - 2867
EP - 2873
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 12
ER -