The discovery raises the hope of personalized preventive treatments for women susceptible to post-menopausal breast cancer.
The new research is among the first to link the cumulative effects of variations in several genes to a woman’s risk of breast and uterine cancer. Individually, the single-letter variations – single-nucleotide polymorphisms (SNPs) – had little impact.
Researchers from Singapore, Sweden and Finland linked 121 SNPs within 15 genes to women’s risk of developing oestrogen receptor (ER)-positive tumours. The variations are in a section of DNA close to a gene responsible for processing oestrogen.
The new associations were found in two different cancers and two different populations, suggesting the findings were not random chance events.
Dr Edison Liu – a lead scientist on the study – commented that each single-letter variation adds only a little to breast cancer risk but that risk increases for women who inherit several harmful SNPs.
It’s like being dealt a bad hand in a poker game,’ he said, adding that ‘this risk is greatly affected by other non-genetic factors like a woman’s reproductive history’ – increasing the complexity of the search for genetic factors.
Dr Liu said it’s unlikely large changes in a single gene would completely explain a woman’s risk. ‘Families carrying major perturbations in the oestrogen receptor or in the genes metabolising oestrogens would most likely die out over generations’, he suggested; therefore, only variations with small effects continue to be inherited.
‘We’re now looking at whether we can produce a model of genetic susceptibility that can explain some of the risk of ER-positive breast cancer,’ Dr Liu added. The model could be used to identify women who would benefit from treatments to reduce their lifetime exposure to oestrogen, such as aromatase inhibitors (drugs that block the conversion of other hormones into oestrogen).
Dr Liu, Executive Director of the Genome Institute of Singapore, will talk about his work at 11.15 am on Tuesday 7 September at the British Society for Human Genetics Annual Conference, which is being held at the University of Warwick.