Wednesday 12 September 2012

Radiogenomics is coming

I posted last week about the emerging field of Immunogenomics. Today I’ve taken a brief look at what is happening in Radiogenomics. Whilst this field is not using NGS in such a comprehensive way I think it can only be a matter of time before it ramps up.

Radiotherapy is an important tool in treating cancer and the impact of genomics on the field was recognised by researchers in Cambridge and Manchester in 2004. Those researchers started the Radiogenomics: Assessment of Polymorphisms for Predicting the Effects of Radiotherapy study (RAPPER) and also helped found the International Radiogenomics Consortium.

The ultimate aim of this consortium is to individualise radiation dose prescription for patients maximising the impact on the tumour whilst minimising normal tissue damage for the patient. They aim to find genomic variants that can help predict how patients will respond to radiotherapy and allow tailoring of treatment. This is somewhat similar to pharmacogenomics approaches used for drugs like Warfarin where SNP genotyping can help establish the correct dose for individual patients. The consortium should make it easier to collect samples for genomic studies and also spur development of methods for radiogenomic research.

The consortium is likely to also learn a lot more about the biology of radiation-induced tissue and DNA damage. Whilst understanding how individuals may respond to radiotherapy is a primary goal, hopefully a better understanding of biology may lead to a list of genes that might be mutated in tumours making them more susceptible to radiotherapy as well.

The Radiogenomics Consotium conducted a GWAS in radiotherapy patients (Independent validation of genes and polymorphisms reported to be associated with radiation toxicity: a prospective analysis study. Lancet Oncol. 2012) to address concerns over how underpowered previous research on late side-effects had been. Late side-effects can have serious impacts on patients and their treatment. This prospective study genotyped 92 SNPs (selected from previous studies) in 1600 breast and prostate cancer patients using the Fluidigm 96.96 Dynamic Arrays. None of the SNPs previously reported to have a significant associations with radiation sensitivity were confirmed. The consortium suggested that the previous associations were “dominated by false-positive associations due to small sample sizes, multiple testing, and the absence of rigorous independent validation attempts in the original studies”.

As the costs of sequencing continue to fall and as associations are found it is likely that NGS will become a more important tool for the consortium. Longitudinal studies of cancer patients can be incredibly revealing and comparison of cancer genome and normal genome with radiotherapy follow up data is likely to yield interesting results.

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