RT Journal
A1 Smirnov, Denis A.
A1 Brady, Lauren
A1 Halasa, Krzysztof
A1 Morley, Michael
A1 Solomon, Sonia
A1 Cheung, Vivian G.
T1 Genetic variation in radiation-induced cell death
JF Genome Research 
JO Genome Research 
YR 2012 
FD February 01 
VO 22 
IS 2 
SP 332 
OP 339 
DO 10.1101/gr.122044.111 
UL http://genome.cshlp.org/content/22/2/332.abstract 
AB Radiation exposure through environmental, medical, and occupational settings is increasingly common. While radiation has harmful effects, it has utility in many applications such as radiotherapy for cancer. To increase the efficacy of radiation treatment and minimize its risks, a better understanding of the individual differences in radiosensitivity and the molecular basis of radiation response is needed. Here, we integrated human genetic and functional genomic approaches to study the response of human cells to radiation. We measured radiation-induced changes in gene expression and cell death in B cells from normal individuals. We found extensive individual variation in gene expression and cellular responses. To understand the genetic basis of this variation, we mapped the DNA sequence variants that influence expression response to radiation. We also identified radiation-responsive genes that regulate cell death; silencing of these genes by small interfering RNA led to an increase in radiation-induced cell death in human B cells, colorectal and prostate cancer cells. Together these results uncovered DNA variants that contribute to radiosensitivity and identified genes that can be targeted to increase the sensitivity of tumors to radiation.