A DNA array (image: Michele Studer, Wellcome Images CC by-nc-nd 4.0)
A single letter in a strand of DNA within tumours is linked to longer survival times for some patients treated for bowel cancer, a new study reveals.
A team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust found that a switch of one letter of DNA coding for a tiny piece of microRNA was linked to increased survival rates for rectal cancer, compared with patients who didn’t have the variation.
But patients without the variation who received a targeted treatment called cetuximab were as likely to survive long-term as those who had the variation and received normal treatment.
The study could help doctors to give patients the most appropriate treatment for their cancer, as a means of maximising survival rates while minimising side-effects.
The research was published in the journal Carcinogenesis, and was funded by Cancer Research UK, the European Union and the Peter Stebbings Memorial Charity, with additional support from the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden and the ICR.
Tiny variations in DNA
A single nucleotide polymorphism (SNP) is a variation to one nucleotide of DNA that occurs at a specific position in the genome.
SNPs in a particular microRNA called miR-608 have been linked to improved prognosis for some patients with bowel cancer, but it’s been unclear how this variation affects patients’ response to cancer drugs.
Researchers at the ICR and The Royal Marsden analysed tumour samples from 155 patients treated for advanced rectal cancer for SNPs in miR-608, to see if some patients might benefit from additional treatments.
They found that for patients treated using a combination of chemotherapy and radiotherapy, a SNP which changed a letter of DNA in mir-608 from C to G was associated with better outcomes than in patients without this variation.
Rectal cancer patients with the variation had an 82.1% chance of surviving their disease for five years, compared with 60.7% for patients without the variation.
When the group without the variation received the targeted treatment cetuximab as well, the researchers saw five-year survival rates increase to 82.2%.
Variations 'could guide treatment'
The findings show that adding cetuximab to treatment for rectal cancer patients with the standard genotype could improve clinical outcomes.
Study leader Dr Nicola Valeri, Leader of the Gastrointestinal Cancer Biology and Genomics Team at the ICR and a Consultant at The Royal Marsden, said: “Our study is the latest to show the importance of microRNAs for regulating elements of cancer's behaviour and response to treatment.
“We found that a single-letter variation in a microRNA gene appeared to be linked to significantly better outcomes from rectal cancer. What was particularly encouraging was that other patients without this genetic variation saw their outcomes improve to the same kind of level when they were additionally treated with a targeted cancer drug.
“It opens up the possibility that we can use variations in microRNA to guide treatment choices.”