Identifying potential modifiers of hereditary breast cancer risk in a large African American family

Abstract

Next-generation sequencing technology has advanced such that research discoveries can be accelerated. In the area of hereditary breast cancer genetics specifically, known breast cancer susceptibility genes only contribute to approximately 35% of hereditary breast cancer cases. Additionally, the majority of the findings reported have been discovered in largely Caucasian cohorts. Given that African Americans are underrepresented in research, and are disproportionately affected by research and healthcare disparities, an intentional effort must be made to include this population in research studies. The Alabama Hereditary Cancer Cohort (AHCC) was established as an effort to recruit and study underserved and underrepresented individuals in Alabama. The AHCC provides a diverse cohort for the study of the genetic risk of breast, ovarian, and prostate cancer using a next-generation sequencing panel, B.O.P. (Breast, Ovarian, and Prostate). This panel permits the elucidation of potential novel hereditary breast cancer risk modifiers. This panel was used to investigate a large African American family in the AHCC. Results show how variants in a prostate cancer susceptibility gene, MAD1L1, are associated with early-onset/hereditary African American breast cancer risk and modify risk in individuals with a pathogenic variant in a clinically significant breast cancer susceptibility gene.