We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Inherited Variants in BLM and the Risk and Clinical Characteristics of Breast Cancer.
- 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
- Abstract
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.
- Subjects
BREAST tumors; CONFIDENCE intervals; GENES; GENETIC mutation; BLOOM syndrome; DESCRIPTIVE statistics; ODDS ratio; GENETICS
- Publication
Cancers, 2019, Vol 11, Issue 10, p1548
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers11101548