Common Genetic Variation and Breast Cancer Risk-Past, Present, and Future

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 27; no. 4; pp. 380 - 394
• Main Authors: Lilyquist, Jenna, Ruddy, Kathryn J, Vachon, Celine M, Couch, Fergus J
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research, Inc 01.04.2018
• Subjects: Biomarkers; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Breast cancer; Breast Neoplasms - genetics; Checkpoint Kinase 2 - genetics; Epidemiology; Female; Genetic diversity; Genetic Loci; Genetic Predisposition to Disease; Genetics; Genome-wide association studies; Genome-Wide Association Study - history; Genome-Wide Association Study - trends; Genomes; Health risk assessment; Health risks; History, 21st Century; Humans; Medical History Taking; Mutation; Polymorphism, Single Nucleotide; Risk Assessment - methods; Single-nucleotide polymorphism
• ISSN: 1055-9965; 1538-7755; 1538-7755
• DOI: 10.1158/1055-9965.EPI-17-1144

Breast cancer is the most common cancer among women in the United States, with up to 30% of those diagnosed displaying a family history of breast cancer. To date, 18% of the familial risk of breast cancer can be explained by SNPs. This review summarizes the discovery of risk-associated SNPs using candidate gene and genome-wide association studies (GWAS), including discovery and replication in large collaborative efforts such as The Collaborative Oncologic Gene-environment Study and OncoArray. We discuss the evolution of GWAS studies, efforts to discover additional SNPs, and methods for identifying causal variants. We summarize findings associated with overall breast cancer, pathologic subtypes, and mutation carriers ( , and ). In addition, we summarize the development of polygenic risk scores (PRS) using the risk-associated SNPs and show how PRS can contribute to estimation of individual risks for developing breast cancer.