Genome-Wide Association Studies Identify Potential Epistatic Effects Contributing to Breast Cancer Susceptibility

Strategic Insights -

New research out of Edmonton, Canada, suggests that genome-wide association studies (GWASs) can identify low-penetrance common variants associated with breast cancer susceptibility. While GWASs primarily focus on single-locus effects, gene-gene interactions, or epistasis, are also assumed to contribute to the genetic risks for complex diseases, including breast cancer. Researchers at Cross Cancer Institute aimed to investigate the potential SNP-SNP interactions contributing to breast cancer susceptibility by selecting SNPs showing single-locus effects with weak statistical significance and replicating them in an independent set of breast cancer cases and controls.

Key Takeaways:

  • The study identified 17 SNPs related to DNA repair, modification, and metabolism pathway genes, which were selected based on prior knowledge of their potential role in breast carcinogenesis.
  • Two two-way SNP-SNP interactions, APEX1-rs1130409 and RPAP1-rs2297381, and MLH1-rs1799977 and MDM2-rs769412, were observed in logistic regression, conferring elevated risks for breast cancer.
  • The study provided a framework for evaluating SNPs showing statistically weak but reproducible single-locus effects for epistatic effects contributing to disease susceptibility.
  • The study design included predominantly Caucasian women (2,795 cases and 4,505 controls) from Alberta, Canada.

Statistics:

  • 17 SNPs related to DNA repair, modification, and metabolism pathway genes were selected for the study.
  • Two two-way SNP-SNP interactions were observed in logistic regression, conferring elevated risks for breast cancer.
  • The study included 2,795 breast cancer cases and 4,505 controls from Alberta, Canada.

Sources:

  • Assessing SNP-SNP interactions among DNA repair, modification and metabolism related pathway genes in breast cancer susceptibility. Plos One, 2014;8(6):e64896. (Public Library of Science - www.plos.org; Plos One - www.plosone.org)