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Genetic biomarkers associated with pain flare and dexamethasone response following palliative radiotherapy in patients with painful bone metastases

  
@article{APM16557,
	author = {Anthony Furfari and Bo Wan and Keyue Ding and Andrew Wong and Liting Zhu and Andrea Bezjak and Rebecca Wong and Carolyn Wilson and Carlo DeAngelis and Azar Azad and Edward Chow and George Charames},
	title = {Genetic biomarkers associated with pain flare and dexamethasone response following palliative radiotherapy in patients with painful bone metastases},
	journal = {Annals of Palliative Medicine},
	volume = {0},
	number = {0},
	year = {2017},
	keywords = {},
	abstract = {Background: In patients who receive palliative radiation therapy (RT) for painful bone metastases, 40% experience a transient increase in pain known as a pain flare. Prophylactic dexamethasone has been shown to reduce pain flare incidence to 25%. We aimed to identify DNA biomarkers associated with pain flare and dexamethasone response. 
Methods: Daily pain levels were recorded by 81 patients who received a single 8 Gy RT for painful bone metastases, of which 50 also received prophylactic dexamethasone. To identify single-nucleotide variants (SNVs), patient saliva samples obtained at day of RT were sequenced for 4,813 disease-associated genes, then filtered for genes associated with inflammation, radiation or immune response, and DNA damage. Significant SNVs (PT) to 0.85 (TSEN54 rs62088470 C>G). 
Conclusions: Significant SNVs associated with pain flare were found in genes with functions in biosynthesis (DHODH, PECR), lipid excretion and metabolism (UGT2A1/2, VLDLR), and intracellular signalling (DNM2, SEC23A). Significant SNVs associated with dexamethasone response were from genes involved in extracellular matrix (HAS1, ADAMTS16) and cytoskeleton regulation (GAS2L2). Identification of SNVs predictive of pain flare and dexamethasone response enables targeted prophylactic therapy according to a patient’s predisposed response.},
	url = {http://apm.amegroups.com/article/view/16557}
}