Inherited Variants in BLM and the Risk and Clinical Characteristics of Breast Cancer

Bloom Syndrome is a rare recessive disease which includes a susceptibility to various cancers. It is caused by homozygous mutations of the BLM gene. To investigate whether heterozygous carriers of a BLM mutation are predisposed to breast cancer, we sequenced BLM in 617 patients from Polish families...

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Bibliographic Details
Published in:Cancers 2019-10, Vol.11 (10), p.1548
Main Authors: Kluźniak, Wojciech, Wokołorczyk, Dominika, Rusak, Bogna, Huzarski, Tomasz, Kashyap, Aniruddh, Stempa, Klaudia, Rudnicka, Helena, Jakubowska, Anna, Szwiec, Marek, Morawska, Sylwia, Gliniewicz, Katarzyna, Mordak, Karina, Stawicka, Małgorzata, Jarkiewicz-Tretyn, Joanna, Cechowska, Magdalena, Domagała, Paweł, Dębniak, Tadeusz, Lener, Marcin, Gronwald, Jacek, Lubiński, Jan, Narod, Steven A., Akbari, Mohammad R., Cybulski, Cezary
Format: Article
Language:English
Subjects:
Age
BLM gene
Bloom's syndrome
Breast cancer
DNA damage
Hypotheses
Jewish people
Mutation
Proteins
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Summary:Bloom Syndrome is a rare recessive disease which includes a susceptibility to various cancers. It is caused by homozygous mutations of the BLM gene. To investigate whether heterozygous carriers of a BLM mutation are predisposed to breast cancer, we sequenced BLM in 617 patients from Polish families with a strong family history of breast cancer. We detected a founder mutation (c.1642C>T, p.Gln548Ter) in 3 of the 617 breast cancer patients (0.49%) who were sequenced. Then, we genotyped 14,804 unselected breast cancer cases and 4698 cancer-free women for the founder mutation. It was identified in 82 of 14,804 (0.55%) unselected cases and in 26 of 4698 (0.55%) controls (OR = 1.0; 95%CI 0.6–1.6). Clinical characteristics of breast cancers in the BLM mutation carriers and non-carriers were similar. Loss of the wild-type BLM allele was not detected in cancers from the BLM mutation carriers. No cancer type was more common in the relatives of mutation carriers compared to relatives of non-carriers. The BLM founder mutation p.Gln548Ter, which in a homozygous state is a cause of Bloom syndrome, does not appear to predispose to breast cancer in a heterozygous state. The finding casts doubt on the designation of BLM as an autosomal dominant breast cancer susceptibility gene.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers11101548