Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients

Abstract

Abstract Background The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity. Methods Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more (n = 180), low grade group were grade 1 or less (n = 180). Pooled genomic DNA (gDNA) (n = 90 from each group) was screened using 23,244 microsatellites. Markers with different inter-group frequencies (Fisher exact test P Results Forty-seven markers had positive association values; including one in the SEMA3A promoter region (P = 1.24 × 10-5). SEMA3A knockdown enhanced radiation resistance. Conclusions This study identified 47 putative radiosensitivity markers, and suggested a role for SEMA3A in radiosensitivity.