A new study could help to answer an important riddle in our understanding of genetics: why research to look for the genetic causes of common diseases has failed to explain more than a fraction of the heritable risk of developing them.
The study published in the journal PLOS Genetics and led by scientists at The Institute of Cancer Research, London, shows for the first time in cancer that some common genetic variants could actually be indicators of the presence of much more influential rare mutations that have yet to be found.
Study co-leader Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research and Honorary Clinical Consultant at The Royal Marsden NHS Foundation Trust, said: "One important unanswered question in cancer genetics - and in genetics of common disease more generally - is why the genetic mutations we've discovered so far each seem to have such a small effect, when studies of families have shown that our genetic make-up has a very large influence on our risk of cancer.
"Our study is an important step forward in our understanding of where we might find this 'missing' genetic risk in cancer. At least in part, it might lie in rarer mutations which current research tools have struggled to find, because individually each does not affect a large number of people."
Study co-leader Dr Zsofia Kote-Jarai, Senior Staff Scientist at The Institute of Cancer Research (ICR), said: "As far as we are aware, this is the first known example of a 'synthetic association' in cancer genetics. Our study does not imply how widespread this phenomenon may be, but it demonstrates the importance of identifying the causal genetic changes behind the many common variants that have already been shown to influence risk of disease."