Gene discovery sheds light on hereditary breast cancer

US Researchers have discovered a gene that could lead to an explanation for some cases of inherited breast cancer in families who have tested negative for BRCA1; a well-known gene responsible for less than 50 per cent of inherited breast cancer cases, say the authors of the study.

Published in the journal Science, three teams of researchers have identified a possible new breast cancer gene, RAP80, showing it to be essential for BRCA1 to carry out its normal function in DNA repair.

'The genetic basis of breast cancers in other families has been largely unknown', explains Roger Greenberg, senior author of one of the papers. 'These families aren't able to make informed choices about screening and treatment, prophylactic or otherwise, the way the BRCA families can'.

It's a constant battle for the body to repair the DNA damage which occurs naturally in all cells. Previous studies have shown that the cells in people who have an abnormal BRCA1 gene are unable to carry out DNA repair properly, resulting in the accumulation of potentially cancer-causing DNA damage.

By using a laser to cause DNA damage to specific sites in cells, the researchers have shown that proteins produced by the RAP80 and BRCA1 genes both accumulate at the site of damage in normal cells, but not in cells with an abnormal RAP80 gene. They believe that this could be because the RAP80 gene helps BRCA1 to identify areas of DNA in need of repair, by binding to these sites.

'With this current discovery, we have made significant new insights into the molecular mechanism by which BRCA1 recognizes sites of DNA damage that breast-cancer-causing mutated forms of BRCA1 cannot recognize', says Greenberg. 'Now we have gained a partial understanding of the molecular basis between cancer-causing BRCA1 failures to fix DNA damage versus normal BRCA1's ability to fix DNA damage'.

Speaking to the Guardian newspaper, Ed Young, a scientist form Cancer Research UK said: 'RAP80 attaches to a region in BRCA1 and then also attaches to damaged DNA; it acts as a go between. At the moment, that has no clinical implications but what they're saying is that RAP80 could possibly be a breast cancer gene'.

During the 1990's the discovery of the BRCA 1 and BRCA2 genes, which can cause women to have up to an 80 per cent chance of developing breast cancer if abnormal, have been the most significant advances in our understanding of the genetic basis of breast cancer. Although further research is needed, the discovery of a link between RAP80 and BRCA1 may in future help to identify women at high risk from breast cancer, who do not have BRCA abnormalities.