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

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 < 0.05) were analyzed using the remaining pooled gDNA. Silencing RNA treatment was performed in cultured normal human skin fibroblasts.

Results

Forty-seven markers had positive association values; including one in the SEMA3A promoter region (P = 1.24 x 10(-5)). SEMA3A knockdown enhanced radiation resistance.

Conclusions

This study identified 47 putative radiosensitivity markers, and suggested a role for SEMA3A in radiosensitivity.

SUBMITTER: Michikawa Y 

PROVIDER: S-EPMC2928773 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature