title: Genetic variation in radiation-induced cell death.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Denis A
authors.initials: DA
authors.lastname: Smirnov
authors.forename: Lauren
authors.initials: L
authors.lastname: Brady
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Halasa
authors.forename: Michael
authors.initials: M
authors.lastname: Morley
authors.forename: Sonia
authors.initials: S
authors.lastname: Solomon
authors.forename: Vivian G
authors.initials: VG
authors.lastname: Cheung
mesh_terms: D017209:Apoptosis; D016923:Cell Death / Q000235:genetics*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000528:radiation effects; D020868:Gene Silencing; D008040:Genetic Linkage; D014644:Genetic Variation; D005828:Genetics, Population; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011836:Radiation Tolerance / Q000235:genetics*