Breast Cancer Risk Gene Candidates Found by Multi-Ancestry Low-Frequency Variant Analysis

In Genome Medicine, an international team led by investigators at University College London, the Alan Turing Institute, and other centers describe breast cancer risk gene candidates found by considering low-frequency genetic variants in a large group of diverse breast cancer cases and controls. Using OncoArray genotypes, the researchers compared low-frequency variants in protein-coding and regulatory sequences in cancer-related genome regions within nearly 83,500 breast cancer cases and almost 59,200 control individuals of African, Asian, European, Hispanic, or Latin American ancestry who were enrolled in dozens of past studies by the Breast Cancer Association Consortium. The search uncovered suspicious variants in genes both with and without prior ties to breast cancer risk within or across ancestry groups — a set that included 14 genes corresponding to breast cancer risk in individuals of European ancestry and genes implicated in other cancer types. "Adopting a recently proposed aggregation method that combines variants in coding and regulatory regions, we were able to replicate and extend previously reported findings," the authors report. "This aggregation method helps identify target genes of previously reported single-marker associations and uncovers additional associations that were missed by other methods."