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Blood test could pick up genetic echoes of lifestyle risk for cancer

A blood test could one day uncover the genetic ‘echoes’ from past activity such as smoking which could increase a person’s chance of developing cancer years later, a new study led by Professor Montserrat Garcia-Closas at the ICR suggests.

Scientists at the ICR have shown that blood tests can accurately assess long-term levels of DNA methylation – the tags placed on genes which help turn their activity down.

They found that markers for DNA methylation in white blood cells remained stable over several years, opening the possibility that these could be used to indicate past exposure to factors that increase cancer risk.

DNA methylation increased with age, but decreased with past smoking. The findings suggest that a blood test could be used to assess a patient’s past exposure to risk factors for cancer through their lifestyle and environmental exposures.

The study, which was published in the journal Cancer Epidemiology, Biomarkers and Prevention, was funded by Breakthrough Breast Cancer and the National Institute for Health Research Biomedical Research Centre at The Royal Marsden and the ICR.

As well as accumulating genetic mutations, cancer cells also build up so-called epigenetic changes – chemical modifications to DNA which don’t change the sequence of the genetic code but do affect the activity of genes.

Previous studies have shown that smoking decreases DNA methylation in white blood cells, so epigenetic changes could be a biological marker for exposures that can lead to cancer – but it’s been unclear whether changes in DNA methylation remain consistent over time.

Scientists at the ICR measured levels of DNA methylation in white blood cells in sets of blood samples from 92 healthy women taken six years apart, to investigate changes in DNA methylation over time.

The researchers found that from a total of 355,633 regions of DNA processed, there were 61,593 methylated DNA markers that varied across the group studied but which remained consistent within each individual over time.

They saw that some levels of DNA methylation increased with both the age and weight of the patient, and three regions of methylated DNA also showed significant associations with smoking status.

Patients who had smoked during their lives displayed lower levels of methylation in these three DNA regions than patients who had never smoked, while methylation levels were higher for patients who had quit smoking earlier, indicating the impact of past smoking.

The findings show that methylation levels of some regions of DNA stay stable over time, which means a blood test could indicate whether exposures have occurred in the past.

Study leader Professor Garcia-Closas, Professor of Epidemiology at the ICR, said: “Environmental or lifestyle factors such as smoking can leave behind traces of their impact on our cells, like echoes from the past. DNA methylation changes the activity of genes within our cells and there is increasing evidence that it plays an important role in cancer.

“Our study shows that a blood test taken at one point in time is able to stably assess that person’s levels of DNA methylation in some regions. We found that DNA markers related to smoking can be detected many years after stopping smoking, suggesting that a blood sample could provide an assessment of past lifestyle exposures.

“Our results support the conduct of further studies in larger populations to determine the potential value of methylation DNA markers measured in blood to predict risk of developing cancer.”

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