QIMR scientists have played a key role in the world’s largest study of its kind, identifying more than 60 regions of the genome that can increase a person’s risk of breast, prostate and ovarian cancer.
Head of QIMR’s Cancer Program, Professor Georgia Chenevix-Trench, said the study of more than 200,000 people could lead to new treatments, targeted screening and a greater understanding of how the cancers develop.
“QIMR has played a major role in research with enormous consequences,” Professor Chenevix-Trench said.
“We’ve gone beyond gene discovery to now having a much better understanding of how these cancer genes function. This is a major step forward in the battle to find new treatments.
“We are also now on the verge of developing tests to complement breast screening, to identify those people at greatest risk.”
The international study was led by Cambridge University and relied heavily on QIMR’s multi-team input. The research was looking for “typographical errors” – called single nucleotide polymorphisms (SNPs) – that flag the presence of nearby genes, or genetic switches, which may increase the risk of developing cancer.
By studying the DNA makeup of more than 100,000 people with cancer and 100,000 without, the scientists found “typos” which were more common in people with breast, prostate or ovarian cancers.
“By themselves, each of these typos increases the risk of cancer by a very small amount,” Professor Chenevix-Trench said.
“But the small number of women in the population who have a large number of them are three times more likely to develop breast cancer than the women who carry an average number of typos.”
For breast cancer, the researchers found 49 SNPs, more than doubling the number found in previous studies. They were found in regions that have been linked to other cancers, suggesting they share underlying mechanisms that can cause cancer.
Scientists already knew that women with the BRCA gene faults are at greater risk of breast and ovarian cancers. This new study has established that the 5% of the women who carry the BRCA1 or BRCA2 fault and also have many of the “typos”, have more than an 80% chance of developing breast cancer by the time they’re 80.
“The next step is to develop ways to bring this information into the clinic so that women with spellings mistakes in BRCA1 or BRCA2 can be given their individual risk rating,” Professor Chenevix-Trench said.
The scientists also found 26 genetic spelling mistakes in prostate cancer, but believe this is just the tip of the iceberg and there could be more than 2000 regions that influence a man’s chance of getting the disease.
Nine new gene regions were also found in ovarian cancer, one of which was already linked by QIMR researchers to prostate and endometrial cancer. This suggests further research will provide fresh insights into similarities between different cancers.
The 12 studies which make up this research are published simultaneously in the current issues of Nature Genetics, Nature Communications, American Journal of Human Genetics, PLOS Genetics, and Human Molecular Genetics.
The QIMR scientists’ work was funded by the National Health and Medical Research Council and the National Breast Cancer Foundation.
The Collaborative Oncological Gene-environment Study (COGS) involved more than 200 research groups around the world including Professor Chenevix-Trench’s lab, Dr Penny Webb from QIMR’s Gynaecological Cancers Group, and Dr Amanda Spurdle from QIMR’s Molecular Cancer Epidemiology Laboratory.
It tapped into four international consortia, including the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) which was founded by Professor Chenevix-Trench. Dr Stacey Edwards and Dr Juliet French, newly recruited to QIMR, have taken a lead role in uncovering how two of the new breast cancer susceptibility genes might work.