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

Abstract

Bloom Syndrome is a rare recessive disease which includes a susceptibility to various cancers. It is caused by homozygous mutations of the <i>BLM</i> gene. To investigate whether heterozygous carriers of a <i>BLM</i> mutation are predisposed to breast cancer, we sequenced <i>BLM</i> 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 <i>BLM</i> mutation carriers and non-carriers were similar. Loss of the wild-type <i>BLM</i> allele was not detected in cancers from the <i>BLM</i> mutation carriers. No cancer type was more common in the relatives of mutation carriers compared to relatives of non-carriers. The <i>BLM</i> 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 <i>BLM</i> as an autosomal dominant breast cancer susceptibility gene.