Decades of research have shown that rare highly penetrant mutations can promote tumorigenesis, but it is still unclear whether variants observed at high-frequency in the broader population could modulate the risk of developing cancer. Genome-wide Association Studies (GWAS) have generated a wealth of data linking single nucleotide polymorphisms (SNPs) to increased cancer risk, but the effect of these mutations are usually subtle, leaving most of cancer heritability unexplained. Understanding the role of high-frequency mutations in cancer can provide new intervention points for early diagnostics, patient stratification and treatment in malignancies with high prevalence, such as breast cancer. Here we review state-of-the-art methods to study cancer heritability using GWAS data and provide an updated map of breast cancer susceptibility loci at the SNP and gene level.

Department of Clinical Studies Faculty of Medicine University of Ostrava Ostrava Czech Republic

Institute of Quantitative Biology Biochemistry and Biotechnology SynthSys School of Biological Sciences University of Edinburgh Edinburgh EH9 3BF UK

Molecular Oncology Laboratories Department of Oncology The Weatherall Institute of Molecular Medicine University of Oxford Oxford UK

Nuffield Department of Clinical Laboratory Sciences University of Oxford John Radcliffe Hospital Oxford UK

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