Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients.
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.
Michikawa
Yuichi
Y
RadGenomics Project, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
Suga
Tomo
T
Ishikawa
Atsuko
A
Hayashi
Hideki
H
Oka
Akira
A
Inoko
Hidetoshi
H
Iwakawa
Mayumi
M
Imai
Takashi
T
D005347:Fibroblasts; D006801:Humans; D018895:Microsatellite Repeats; D009369:Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000235:genetics*