28 May 2007The GuardianPolly Curtis
A mammogram used to screen for signs of breast cancer. Photograph: Lester Lefkowitz/Getty Images
Scientists have discovered four genes which, if faulty, can increase a woman's chance of developing breast cancer - by up to 60% in the case of two of the genes. This helps explain why women with a close relative with breast cancer are twice as likely to develop the disease, and offers the hope of a test in the near future. The scientists also believe the techniques used will help them unravel other cancers.
Karol Sikora, a leading cancer specialist, said of the studies published online in Nature and Nature Genetics last night: "This set of incredible papers points to the future understanding [of] the genetics of cancer."
It is the most significant discovery in the field since the 1990s, when scientists identified two rare genes, BRCA1 and BRCA2, which make carriers likely to develop breast cancer. An international coalition of researchers led by Cancer Research UK at Cambridge University has proved the theory that geneticists have been working on ever since: that most familial patterns of breast cancer can be explained by myriad smaller genetic effects.
Breast cancer is twice as common in those who have a close relative who develops it due to a fault in a gene, although the presence of a faulty gene does not mean that cancer will definitely occur.
The scientists trawled large parts of the genome in 800 people. They identified 11,000 "tags", or blocks of DNA which point to genes, which were more common in women with breast cancer and studied them in 8,000 more women. In the final process, which involved 40,000 women, they narrowed the search down to five tags which were significantly more common among women with breast cancer than those without. The tags pointed them to four genes which they believe are responsible for the increased breast cancer risk among the patients studied. Scientists expect that they will find a fifth.
Two of the genes identified, FGFR2 and TNRC9, are thought to increase the risk of breast cancer by about 20% in women who carry one faulty copy of a gene and by between 40% and 60% in those who carry two faulty copies. The lifetime risk for women with two faulty copies in either of these two genes would rise from one in 11 to around one in six or seven. The other two genes increase risk by 10% if there is one fault.
A maximum 10% of breast cancers have a genetic element, and the genes scientists know about so far account for 25% of these. The genes identified today account for a further 4% and are responsible for only a small number of breast cancers - up to 179 of the 44,000 diagnosed every year.
The ultimate aim is genetic screening that would band women according to risk. But scientists warn this could create an army of "worried well". They stress that the findings do not merit genetic testing immediately.
The findings do, however, hint at a different cause of familial breast cancers. Three of the new genes are involved in the control of cell growth or cell signalling, mechanisms which have never been linked to breast cancer before.
The author of the study, Douglas Easton, director of Cancer Research UK's Genetic Epidemiology Unit in Cambridge, said: "We're very excited by these results because the regions we identified don't contain previously known inherited cancer genes. This opens the door to new research directions." The techniques used are similar to those which helped identify the genes for obesity last month.
