DNA Methylation Biomarkers for Cancer

In 2019, cancer was the cause of over 10 million deaths globally and was the first or second leading cause of death in 112 countries1,2. One of the primary reasons for such large number of cancer-related deaths is late diagnosis. For example, if breast cancer is diagnosed at stage 1, the survival rate is over 90% but drops to only 66% with a stage 4 diagnosis-3. Thus, early diagnosis is key if we are to reduce cancer-related deaths.

An important means to achieve this is through the development of non-invasive biomarkers for early cancer detection. A biomarker is any molecule or measurable change, whether in the blood, bodily fluids, or tissue, that can be measured and represents a biological process, pathological change, or pharmacological response to therapy. 

DNA methylation biomarkers have garnered considerable interest in the field of cancer detection as they offer incredible potential for non-invasive and early diagnoses.This is because cancer cells exude DNA into blood which can be analysed for methylation patterns that are specific to cancer. DNA methylation offers several advantages as biomarkers. Firstly, DNA methylation can be analysed from various sources such as saliva, blood, urine, stool, etc making it an accessible biomarker. Secondly, DNA methylation patterns are very dynamic and can change in response to treatment, with disease regression, and even with recurrence of disease, thus providing valuable real-time information of intracellular changes in the body. Thirdly, DNA methylation changes can be seen very early in cancer and often in pre-cancerous lesions, which serves as an excellent early detection tool, risk prediction, and population screening. 

Several types of methylation biomarkers have been developed for cancer. The GRAIL Galleri test is a multiple cancer early detection test which is available through prescription in the US and is in clinical trials in the UK. The GALLERI utilises DNA methylation from blood to detect up to 50 cancer types, as early as stage 1. In the UK it was tested in the SYMPLIFY trial, the results of which show that it correctly detected cancers in 66% of the cases (2 out of 3 patients)4. It also provides further valuable additional information on tissue origin of the cancer. The GRAIL biomarker is being further studied in the GALLERI-NHS clinical trial which is due to be completed next year. 

Other multiple cancer early detection have also been approved, such as the OverC multi-cancer detection blood test which was granted expedited development by the FDA and detects 5 different types of cancer. The IVYGeneCore test which is available in South Africa also  detects 5 cancers and has a higher sensitivity than the GRAIL test of 80%.

Another important application of methylation biomarkers is population screening in asymptomatic patients. For example, the WID-CIN test is a cervical cancer screening test that has been tested in Sweden. Compared to current standard screening methods, it detected a higher number of cancer cases. As such, this is now being explored to be incorporated into existing cervical screening programmes. 

In terms of predictive biomarkers, MGMT promoter methylation is shown to be associated with better response to temozolomide in glioma patients. Thus MGMT promoter methylation testing has entered standard of care and management for glioma and is a key factor for selection of treatments for GBM patients. Several MGMT methylation kits are available on the market (Xiamen, LabCorp, Qiagen).

Despite their immense potential, the implementation of DNA methylation biomarkers in clinical practice faces several challenges. Cost, logistical issues, reproducibility, and the integration of biomarkers into existing healthcare guidelines are key hurdles that need to be addressed through collaborative efforts among clinicians, researchers, and industry partners. But with continued research and collaboration, these biomarkers have the potential to revolutionise cancer care, bringing us closer to a future where cancer is detected early and treated effectively, ultimately saving lives.


  1. Sung, H. et al. (2021) ‘Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries’, CA: A Cancer Journal for Clinicians, 71(3). doi: 10.3322/caac.21660.
  2. World Health Organization (2020) ‘Global health estimates for 2020: deaths by cause, age, sex, by country and by region, 2000-2019’, Who, (December). 
  3. Bannister, N. and Broggio, J. (2016) ‘Cancer survival by stage at diagnosis for England (experimental statistics): adults diagnosed 2012, 2013 and 2014 and followed up to 2015’, Produced in collaboration with Public Health England.
  4. Nicholson BD, et. al 2023, Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study. Lancet Oncol. 2023 Jul;24(7):733-743. doi: 10.1016/S1470-2045(23)00277-2. Epub 2023 Jun 20. PMID: 37352875.