Women who delay motherhood until their 30s significantly increase their risk of getting breast cancer, according to the results of a first of its kind gene analysis study.
Researchers from Imperial College London analysed laser-extracted DNA from breast tissue donated by mothers and childless women across a wide age range.
Computer modelling then compared and contrasted their results against a reference genome, enabling researchers to track the development of abnormal cells.
Professor Justin Stebbing, who led the four-year study, said the findings were both “surprising and overwhelming”, but that the genetic sequencing data could contribute to saving lives in the future. He said:
“We now know age and pregnancy work together as potent factors. If a 40-year-old woman gets pregnant, her risk of breast cancer risk is 20 times higher than that of a 20-year-old woman.”
Prof Stebbing noted that the research uncovered rising cell mutation levels in pregnant women entering their 30s, and that 32 years of age was a marker point at which a “much greater number of mutations” appeared. From the age of 35 there is another “notable uptick” in the number of mutations, he said.
“From the billions of data points we see an age-linear accumulation of mutations, but during pregnancy at an older age it is like putting paraffin on a fire – it takes it from linear to a much more random expansion. At the age of 40, we see yet another higher escalation point,”
The study secured access to healthy tissue samples from 29 women, who had donated via the Susan G. Komen Tissue Bank in Indiana, America. Prof Stebbing said:
“This is a very high number of samples for this kind of study. Given the extraordinary amount of information we collect from each woman, unravelling three billion letters of DNA in each, it all adds up to a colossal treasure trove of information that we now release to the world.”
In a world first, the study analysed completely healthy breast tissue, enabling insight into the development of cell mutations at the earliest stages.
Prof Stebbing noted that previous papers had to rely on tissue taken close to a cancer or, for example, from an adjacent breast in a sick patient. He stated further:
“Normal tissue gave us a crucial opportunity to evaluate cellular degradation whilst factoring in age and pregnancy. There are two types of mutations we typically see in cancer cells, and we refer to these as passengers and drivers.
“Drivers are the more dangerous ones and, surprisingly, it was these very ones that we spotted in the older pregnant women – a linear increase in the epithelial cells with age.
“We have discovered that a combination of late pregnancy and age foster a huge number of cell mutations. If you take a woman who has never had kids, the mutational burden goes up and up with age.
“However, we now know what happens is that with late pregnancy you get an enrichment on top of that, of what we call mutated clones – groups of cells with important mutations in them.”
The paper was published on an open access pre-print repository this week and will now be subject to a peer-review process. It is the first study to demonstrate precisely how pre-cancerous mutations develop in the breast and where.
Dr Biancastella Cereser, who designed the study with Prof Stebbing, told The Telegraph:
“We biopsied branches of the duct, the more functional part of the breast, but we also looked at epithelium cells, where cancer usually starts. We extracted DNA from there and also the surrounding area of tissue.
“The colon and some other organs have been sequenced but not the breast, cancer there is more complex because of the influence of hormonal changes.”
The positive impact from the study could be twofold, Prof Stebbing said, adding:
“With this kind of information, we can start to identify the specific women who need to have their breasts closely monitored during pregnancy.
“Secondly, this data brings us another step forward to a future where cancer patients will be prescribed medication specifically suited to their genes.”