A study of blood samples collected up to nine years before a cancer diagnosis found changes in the DNA that captured the body's response to early traces of cancer development.
The findings, published recently in Cell Genomics , build on other recent work by researchers at the University of Toronto, Ontario Institute for Cancer Research and Oxford Population Health and are aimed at identifying the earliest signs of cancer development using a highly sensitive blood profiling tool that captures DNA changes.
The study was led by Nicholas Cheng, a PhD graduate from the department of molecular genetics in U of T's Temerty Faculty of Medicine, under the supervision of Philip Awadalla, a professor at Oxford Population Health and the University of Oxford's Big Data Institute who holds a status appointment at U of T's Temerty Faculty of Medicine.
The research team also included Daniel De Carvalho, Scott Bratman and David Cescon - all researchers at Princess Margaret Cancer Centre, University Health Network and Temerty Medicine.
Cancer remains the second leading cause of death globally, with deaths often resulting from a late diagnosis. When cancers are detected early, treatment is more likely to be successful and patients have a better chance of surviving.
Routine screening tests remain limited to a few cancers, such as Pap smears for cervical cancer and stool tests for colorectal cancer. For other cancers, early detection varies in effectiveness - from radiological imaging to detect tumours, to examining a tissue sample to look for cellular abnormalities.
However, recent developments in the use of liquid biopsies offer the possibility of detecting cancer in its earliest stages using minimally invasive blood or urine tests.
DNA reveals markers for people at high risk
Currently, liquid biopsies are mainly used after a cancer diagnosis to find and analyze DNA from existing tumours or to track potential recurrence. For this study, the researchers looked at blood samples collected from individuals who were months or years away from a cancer diagnosis to understand whether their DNA would reveal the earliest biological changes associated with cancer development.
They used stored blood samples from 491 participants in the Ontario Health Study who were cancer-free when their blood was collected. Some subsequently developed breast or prostate cancer, while others remained cancer-free. The researchers looked for differences in chemical patterns in the DNA known as methylation. These tiny chemical tags act like switches that control gene activity linked to functions such as cell growth, immune function and inflammation.
They found that prostate cancer produced the strongest early signal through methylation changes in DNA regions called silencers, which normally help genes switch off. Using these markers, the researchers could identify people at high risk of developing prostate cancer five to eight years before a diagnosis. With no current population-wide screening program for prostate cancer, the authors suggest that this type of testing could eventually help identify people in need of more proactive screening while reducing unnecessary testing in low-risk individuals.
Breast cancer was more difficult to detect but still showed some early signals through methylation changes in DNA regions called enhancers. Although the test's overall accuracy was lower than for prostate cancer, it could still distinguish women at higher and lower risk of developing breast cancer 1.5 to eight years before a diagnosis. The authors note that for breast cancer, the test is unlikely to be accurate enough for population-wide screening but could be useful as a complementary risk-assessment tool.
Blood tests could support future cancer screening
Awadalla said the study represents an important next step in a broader research program using cell-free methylated DNA immunoprecipitation sequencing. Earlier studies established that this approach could detect and classify multiple tumour types , distinguish localized from metastatic prostate cancer and identify advanced breast cancer and its oestrogen-receptor status. Most recently, the team contributed to a resource drawing on nearly 1,300 blood samples from multiple cancer types showing that patterns in DNA methylation can be used to improve detection of a wide range of cancers .
"Together, these studies chart a progression from detecting established tumours to identifying the earliest systemic signals of cancer development - supporting a future in which minimally invasive blood tests could complement existing screening and help identify people who would benefit most from closer surveillance," said Awadalla.
The research was funded by Ontario's Ministry of Colleges, Universities, Research Excellence and Security.
A version of this story originally appeared at Oxford Population Health
