Germline Variation and Breast Cancer Incidence: A Gene-Based Association Study and Whole-Genome Prediction of Early-Onset Breast Cancer (original) (raw)

2018, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Although germline genetics influences breast cancer incidence, published research only explains approximately half of the expected association. Moreover, the accuracy of prediction models remains low. For women who develop breast cancer early, the genetic architecture is less established. To identify loci associated with early-onset breast cancer, gene-based tests were carried out using exome array data from 3,479 women with breast cancer diagnosed before age 50 and 973 age-matched controls. Replication was undertaken in a population that developed breast cancer at all ages of onset. Three gene regions were associated with breast cancer incidence: ( = 1.23 × 10; replication < 1.00 × 10), ( = 3.57 × 10; replication < 1.00 × 10), and ( = 5.49 × 10; replication < 1.00 × 10). Of the 151 gene regions reported in previous literature, 19 (12.5%) showed evidence of association ( < 0.05) with the risk of early-onset breast cancer in the early-onset population. To predict incidenc...