Specific gene increases susceptibility to breast cancer

May 06, 2008

Much work has been done to identify genetic variations that predispose women to breast cancer. Previous work showed that variants in the gene called fibroblast growth factor receptor 2 (FGFR2) were associated with increased risk of the disease, but how these variants translated into increased risk was unknown.

A new paper by Kerstin Meyer and colleagues, published this week in the open-access journal PLoS Biology, shows how specific changes in the FGFR2 gene alter the way regulatory molecules bind to it, leading to increased gene expression, which, in turn, increases the risk of developing breast cancer.

By comparing all of the tiny differences in the genomes of people with breast cancer to those in a control population, FGFR2 had been flagged up as a region of the genome that is consistently different between the two groups. FGFR2 encodes a protein that sits in the membrane of cells and works in a signalling pathway important for cell growth.

This study, conducted in the Cancer Research UK Cambridge Research Institute, has identified just what 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—regulatory proteins that influence gene expression patterns. Because of this additional binding, more FGFR2 protein is produced in cells carrying the mutation and this seems to be enough to increase the risk of cancer a small but significant amount.

Interestingly, the mutation occurs not 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). The two alterations therefore affect the regulation of the gene, but the proteins produced are normal; there is too much of it for the cells to develop as normal, instead becoming cancerous.

Citation: Meyer KB, Maia A-T, O’Reilly M, Teschendorff AE, Chin S-F, et al. (2008) Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer. PLoS Biol 6(5):e108. doi:10.1371/journal.pbio.0060108

Source: Public Library of Science

Explore further: Mayo Clinic offers at-home colon cancer test

add to favorites email to friend print save as pdf

Related Stories

First confirmed common genetic risk factors for breast cancer

May 29, 2007

The most powerful genetic analysis of the DNA codes of over 40,000 women -- including those with breast cancer as well as those without the disease – has uncovered five common genetic variants that increase an individual’s ...

Recommended for you

New tool to probe cancer's molecular make-up

21 hours ago

Scientists have shown how to better identify and measure vital molecules that control cell behaviour – paving the way for improved tools for diagnosis, prediction and monitoring of cancer.

Mayo Clinic offers at-home colon cancer test

Aug 26, 2014

Mayo Clinic is taking another step toward making detection of colorectal cancer as convenient as possible, announcing Monday an at-home kit that arrives and is sent back in the mail, stool sample included.

Finding keys to glioblastoma therapeutic resistance

Aug 26, 2014

Researchers at the University of California, San Diego School of Medicine have found one of the keys to why certain glioblastomas – the primary form of a deadly brain cancer – are resistant to drug therapy. The answer ...

No link found between diverticular disease, cancer

Aug 25, 2014

(HealthDay)—Colonic diverticular disease does not appear to be linked to an increased risk of subsequent colorectal cancer (CRC), according to research published in the August issue of Clinical Gastroenterology an ...

User comments : 0