Vachons team took what they term an agnostic approach to uncovering genes, or gene regulators like microRNA, that are involved in the development of dense breasts. We assume we dont know anything about the biology of the trait and we let the genomes of our participants and their breast densities guide us, Vachon said.
Their method contrasts the traditional candidate gene approach, where scientists look at variations in specific genes thought to be involved with the disease or trait of interest. Such linkage studies have been used to uncover many high-impact risk genes, such as the breast cancer susceptibility genes BRCA1 and BRCA2.
The Mayo researchers performed a genome-wide linkage scan to identify possible chromosome regions in 89 families, part of a multi-generational Minnesota family study that began in 1944 at the University of Minnesota. Blood samples and mammograms were collected and analyzed for 756 female participants; 133 men were also included to help clarify genetic information in their offspring, mothers and sisters. We used the relationship between family members and breast density to inform where a gene might be, Vachon says.
Researchers first studied 403 DNA markers spaced across the genome to determine the amount of genetic information shared at and between each of these genomic signposts and its correlation to breast density as measured on mammography. They found three regions of interest, and narrowed the most promising region further by studying 21 additional, more densely spaced DNA markers. This secondary analysis highlighted one region consisting of approximately 45 known genes on chromosome 5p that was significantly associated with increased breast density.
The researchers then adjusted their analysis to eliminate the contribution of body mass index (BMI), which is a known breast cancer risk factor and also inversely associated with breast density, and found
|Contact: Greg Lester|
American Association for Cancer Research