Researchers at the Cancer Research UK Cambridge Research Institute
have found that changes in a gene called fibroblast growth factor receptor 2 (FGFR2) plays
an important role in determining the risk of breast cancer.
The study authored by Kerstin Meyer and colleagues has
explained how precise changes in the FGFR2 gene change the way regulatory
molecules bind to it, and causes increased gene expression, leading to the
increased risk of developing breast cancer.
The researchers compared all of the tiny differences
in the genomes of people with breast cancer to those in a control population,
and discovered that FGFR2 was found to be different between the two groups.
FGFR2 encodes a protein located in the cell membrane and takes part in a
signalling pathway important for cell growth.
In this study, researchers identified what exactly
these slight genetic changes mean at the molecular level. FGFR2 genes altered
at two specific points have a greater affinity for binding certain
transcription factors, i.e. regulatory proteins that influence gene expression
This additional binding leads to the production of
more FGFR2 protein in cells carrying the mutation and this would suffice for
increasing the risk of cancer in a small but significant amount.
However, the mutation doe not occur in the coding
regions of the genes (the bits translated into protein by cellular machinery),
but rather, in an intron (a region of DNA found amongst the coding bits).
Therefore, these two alterations affect the regulation
of the gene, but the proteins produced are normal. In fact, the mutation is too
much for the cells to develop as normal, and thus they become cancerous.
The study is
published this week in the open-access journal PLoS Biology.