Findings in PLoS Biology shows that these variants on the FGFR2 gene increase transcription factor binding, leading to higher protein expression levels.
Researchers discovered that SNPs in fibroblast growth factor receptor 2 (FGFR2) associated with increased risk of breast cancer alter the way regulatory molecules bind to it. This leads to increased gene expression and thus elevated risk.
The FGFR2 gene encodes a protein in cell membranes and works in a cell growth signaling pathway. Using fine-scale genetic mapping, the investigators found that the mutations occur not in the coding regions of the gene but rather in an intron.
Furthermore, the scientists showed that FGFR2 altered at two specific points has a greater affinity for binding certain transcription factors. Because of this additional binding, more FGFR2 protein is produced in cells carrying the mutation. This seems to be enough to increase the risk of cancer by a small but significant amount, the researchers report.
The investigators involved in this study are from Cambridge Research Institute and the University of Cambridge. The findings is published in the May 6 issue of PLoS Biology.