Journal Article

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

Lener, Marcin, Rudnicka, Helena, Gliniewicz, Katarzyna, Dębniak, Tadeusz, Rusak, Bogna, Szwiec, Marek, Cybulski, Cezary, Cechowska, Magdalena, Kashyap, Aniruddh, Lubiński, Jan, Stawicka, Małgorzata, Wokołorczyk, Dominika, Jakubowska, Anna, Morawska, Sylwia, Akbari, Mohammad R., Stempa, Klaudia, Mordak, Karina, Gronwald, Jacek, Kluźniak, Wojciech, Domagała, Paweł, Jarkiewicz-Tretyn, Joanna, Huzarski, Tomasz, Narod, Steven A.

2019

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Age / BLM gene / Bloom's syndrome / Breast cancer / DNA damage / Hypotheses / Jewish people / Mutation / Proteins