New breast cancer risk genes discovered

Researchers have identified four new breast-cancer-associated genes that could potentially improve clinical screening for women at risk.

The research, published in Nature Genetics and led by scientists at the University of Cambridge and the Université Laval in Quebec, compared genetic variation in the exomes – the parts of the genome that encode genes – of women with and without breast cancer.

Professor Douglas Easton, director of the Centre for Cancer Genetic Epidemiology at the University of Cambridge, who co-led the study, said: 'To our knowledge, this is the largest study of its kind. It was made possible through the use of data from multiple collaborators in many countries, as well as publicly available data from the UK Biobank.'

Breast cancer is the leading global cause of cancer-related mortality in women and affects almost 56,000 people in the UK each year. Current genetic testing for breast cancer includes well-known genes, such as BRCA1 and 2, but only captures a small proportion of the genetic risk for breast cancer.

The researchers conducted a meta-analysis of three large whole-exome sequencing datasets, containing data from 26,000 women with breast cancer and 217,000 without. The datasets included primarily women with European ancestry from eight countries in Europe and Asia. Using these datasets, the scientists found evidence linking four new genes to breast cancer risk: MAP3K1, LZTR1, ATR and BRD1.

'Although most of the variants identified in these new genes are rare, the risks can be significant for women who carry them. For example, alterations in one of the new genes, MAP3K1, appear to give rise to a particularly high risk of breast cancer,' said co-author Professor Jacques Simard from Université Laval. 'Improving genetic counselling for high-risk women will promote shared decision-making regarding risk reduction strategies, screening and determination of treatment options.'

While these findings advance our understanding of breast cancer risk and could provide new insights into biological mechanisms of breast cancer development, the authors also note that the 'majority of 'missing' heritability is likely to be found in the noncoding genome'.

'We need additional data to determine more precisely the risks of cancer associated with variants in these genes, to study the characteristics of the tumours, and to understand how these genetic effects combine with other lifestyle factors affecting breast cancer risks,' added Professor Easton.