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

Abstract

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 (BRCA1, BRCA2, and CHEK2). 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. Cancer Epidemiol Biomarkers Prev; 27(4); 380-94. ©2018 AACRSee all articles in this CEBP Focus section, "Genome-Wide Association Studies in Cancer."

Figure 1

Allelic architecture of SNPs associated with ER-positive breast cancer Odds ratio and effect allele frequency (EAF) of the risk-associated SNP for all SNPs associated with ER-positive breast cancer in the OncoArray meta-analysis (p<5 × 10⁻⁸) (24)

Figure 2

Allelic architecture of SNPs associated with ER-negative breast cancer Odds ratio and effect allele frequency (EAF) of the risk-associated SNP for all SNPs associated with ER-negative breast cancer in the OncoArray meta-analysis (p<5 × 10⁻⁸) (24, 25)