Epigenetic information from cervical smear samples could help detect ovarian and breast cancer

Cells in cervical smear test samples could be used as an indicator for breast and ovarian cancer, and show promise as tools for monitoring cancer risk.

Two new indexes, the Women's risk Identification for Breast Cancer (WID-BC) and Women's risk Identification for Ovarian Cancer (WID-OC), have been developed for identifying patients with breast and ovarian cancer. In two papers, published in the journal Nature Communications, researchers describe how they used cervical cells collected during routine smear tests to develop the indexes. Patients who are at higher risk of developing breast and ovarian cancers also had higher scores on the index, suggesting that they could be used for risk screening.

'Our studies have taken a completely novel approach and evaluate an individual's risk for more than one cancer by assessing several different epigenetic footprints in a single cervical screening sample' said Professor Martin Widschwendter, from University College London's Institute for Women's Health, who was the senior author on both papers.

'The results published today show that our tests can out-perform currently available methods and we are looking forward to running trials to validate these initial findings in large numbers of women.'

To develop the indexes, the researchers performed an epigenome-wide analysis of DNA methylation across tens of thousands of sites on the genome. Nearly 3000 samples from women from sites across Europe were analysed – including 242, 217 and 329 from (respectively) patients with primary ovarian cancer, patients with endometrial cancer, and patients with breast cancer who also have a poor prognosis.

The researchers discovered sites at which the level of methylation detected could be used to create indexes which measure breast and ovarian cancer risk. In order to validate this, researchers tested the index with part of their dataset. The WID-BC correctly identified 76 percent of women who had breast cancer by placing them in the most at risk group according to the index. Meanwhile, the WID-OC identified 71 percent of people under the age of 50, and 55 percent of women over the age of 50, who had ovarian cancer.

Researchers also considered the WID-BC and WID-OC indexes for patients with mutations in the BRCA1 and BRCA2 genes, who have a higher likelihood of developing breast and ovarian cancer. They found that the pattern of methylation was similar for women who had BRCA mutations but had not developed cancer yet, when compared to women with breast cancer with a poor prognosis.

Researchers hope to combine these findings with measures for womb and cervical cancer risk that are currently under development. Together, these four measures could create a single WID-Test. This could act as a risk indicator for all four cancers, which together are responsible for approximately 50 percent of cancer cases in women. However, further studies are needed to understand the predictive power of these indexes.