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DNA methylation predicts cancer risk

Methylation of DNA is a well-established means of gene expression regulation. European researchers discovered that DNA methylation can predict cancer onset and progression.
DNA methylation predicts cancer risk
DNA methylation refers to the covalent addition of a methyl group to the 5-carbon of the cytosine ring. Methylation occurs in DNA regions that are rich in cytosine guanine dinucleotides known as CpG islands. Methylation of CpGs located in the promoter of genes is involved in the regulation of gene expression, while the majority of methylated cytosine lies in transposable repetitive elements (long and short interspersed elements).

Hypomethylation has been associated with reduced chromosomal stability and altered genome function. Similarly, epigenetic alterations can increase the risk of certain diseases including breast cancer. The EU-funded METHYLBRECA (Study on methylation as risk and prognostic factor for breast cancer) project wished to study the role of DNA methylation as a diagnostic and prognostic factor for breast cancer.

Researchers performed genome-wide methylation on DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour material. This proved rather challenging since DNA extracted from FFPE samples is often of low quality and highly degraded compared to that extracted from blood. Analysis of samples from the Melbourne Collaborative Cohort Study led to the identification of a differential methylation profile between tumour samples and the adjacent normal breast tissues.

The same approach was applied to other cancer types, and in particular lung cancer. Scientists performed genome-wide DNA methylation analysis and identified two loci in the AHRR and F2RL3 genes whose methylation levels are strongly associated with lung cancer risk. Interestingly, these two loci appeared to partially mediate the effect of smoking on lung cancer risk. In addition, methylation at another four different genomic locations was inversely associated with lung cancer risk.

Methylation of five of the identified CpGs was lowest in current smokers and increased in former smokers, clearly supporting the growing evidence that smoking may lead to DNA methylation changes. Apart from enhancing the knowledge on cancer biology, these findings open new avenues for the prevention, early detection and treatment of cancer.

Related information


Life Sciences


DNA methylation, cancer, METHYLBRECA, AHRR, F2RL3
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