Pain is one of the most prevalent symptoms among breast cancer survivors, which negatively impact on their quality of life (QOL). Adjuvant radiotherapy (RT) can increase the risk of development or persistence of pain; however, little is known about the mechanisms of RT-related pain or genetic susceptibility. The current study aimed to identify susceptible loci and enriched pathways for clinically relevant pain, which is defined as pain score ≥ 4, at the completion of RT (post-RT pain). We conducted a genome-wide association study (GWAS) of 1,112 breast cancer patients with 1,344,832 tagging SNPs, gene-based analysis using PLINK set-based tests for 19,621 genes, and functional enrichment analysis of a gene list (875 genes having p < 0.05) using NIH DAVID functional annotation module with KEGG pathways and GO terms (n=380). About 29% of patients reported post-RT pain, and 4 SNPs showed suggestive associations; rs16970540 in RFFL or near to LIG3 gene (p=1.7x10-6), rs4584690 and rs7335912 in ABCC4/MPR4 gene (p=5.5x10-6 and p=7.8x10-6, respectively), and rs73633565 in EGFL6 gene (p=8.1x10-6). Gene-based analysis suggested the importance (involvement) of neurotransmitter, olfactory receptor, and cytochrome P450 in post-RT pain, and functional analysis suggested glucuronidation and olfactory receptor activity as the most enriched biological processes/features. With a limited size of sample, this is the first GWA study showing (confirming) that post-RT pain is a complex polygenic trait influenced by many biological processes and functions. If validated in a larger population, the results can provide biological targets for pain management to improve cancer survivor's QOL. Additionally, these findings may be used as predictive biomarkers of personalized pain management.

Citation Format: Eunkyung Lee, Christina Takita, Jean L. Wright, Eden Martin, Susan Slifer, Jennifer Hu. Identification of susceptible loci and enriched pathways for post-radiotherapy pain in breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 231.