Breast cancer gene carriers’ risk ‘amplified’ by additional genes

Many women with a faulty breast cancer gene could be at greater risk of the disease due to extra ‘risk amplifying’ genes, according to research published in this week in the American Journal of Human Genetics.

Cancer Research UK scientists, including lead author Professor Doug Easton at the University of Cambridge, have found that common versions of two genes – FGFR2 and TNRC9 – known to increase breast cancer risk in the general population - also increase the risk in women carrying damaged versions of the BRCA2 gene.

Around one in eighteen women will develop breast cancer by the age of 65. On average, half of women carrying a faulty BRCA2 gene will develop the disease by the age of 70.

This study found that particular combinations of the FGFR2 and TNRC9 genes modify the breast cancer risk in BRCA2 mutation carriers.

Around twenty percent of the BRCA2 mutation carriers have the lowest risk combination of the FGFR2 and TNRC9 genes. The researchers found that their risk is lowered so four in every 10 women in this category are expected to develop breast cancer.

But one per cent of BRCA2 mutation carriers have the highest risk combination of FGFR2 and TNRC9 genes. Seven in every 10 women in this category are predicted to develop the disease.

These findings are the first step in a series of studies hunting for breast cancer susceptibility genes, which aims to better monitor and treat women with a family history of the disease.

Professor Easton, director of Cancer Research UK’s Genetic Epidemiology Unit at the University of Cambridge, said: “This is the first time we have found evidence that common changes in other genes can amplify the risk of breast cancer in women known to have faulty BRCA genes.

“This is the first step in finding a set of genes that modify the risk in BRCA carriers, and may influe nce how we monitor women with a family history of the disease.”

The study brings together results from international research groups looking at a total of more than 10,000 women carrying a BRCA1 or BRCA2 mutation. Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “It’s important to remember that the prevalence of this combination of gene faults is rare in the general population. But advances like this will add to our ability to identify those most at risk for clinical monitoring, detecting the disease earlier in those who develop it.”