@misc{oai:repo.qst.go.jp:00063685,
 author = {Michikawa, Yuichi and Suga, Tomo and Ishikawa, Atsuko and Hayashi, Hideki and Oka, Akira and Inoko, Hidetoshi and Iwakawa, Mayumi and Imai, Takashi and 道川 祐市 and 菅 智 and 石川 敦子 and 岩川 眞由美 and 今井 高志},
 month = {Nov},
 note = {Objectives: Whole genome association study using microsatellite markers has been carried out to search for genes associating with acute adverse effects after radiotherapy for cancer patients. 
\nMaterials and Methods: A total of 360 patients with head and neck, lung, esophageous, breast and cervical cancers were recruited in this study. They were divided into following two groups by the severity of the adverse effects graded by NCICTC version 2 within 3 months after completion of radiotherapy; (1) High Grade Group (HGG) who developed grade 3 or more adverse effect and (2) Low Grade Group (LGG) who developed grade 1 or less adverse effect on any of the endpoints. Each group consisted of 180 patients. Genomic DNA was individually extracted from blood cells of these patients. Two-round scanning of microsatellite markers was conducted using two pools of genomic DNA made of 90 non-overlapping patients in each group. 
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Results and Conclusions:, A total of 21,000 microsatellite markers were scanned using one of the pooled DNA of each group respectively in the first round yielding 3,052 markers with significantly different estimated frequency between the two groups (P-value < 0.05). Reproducibility of these 3052 markers was investigated by the second round scan using the remaining pooled DNA, yielding 159 positive markers (P-value < 0.05). Among them, ten markers locating at the distance within 100 kb from the transcription initiation site of the nearest gene were selected for further individual typing of the all 360 patients. A significant association (P-value = 1.24x105) was displayed by a marker locating at 1,500 bp upstream of Semaphorin 3A gene. Knocking down of this gene expression by siRNA treatment in a human fibroblast culture provided suppression of radiation sensitivity. Semaphorin 3A gene has been reported to encode a secreted protein with a range of functional processes including regulation of axon guidance, cell survival, motility, immune responses, and angiogenesis. It is, thus reasonable to consider this gene to influence adverse effects in several types of cancer patients., The 52nd Annual Meeting of The Japan Radiation Research Society},
 title = {Genome-wide scanning of genetic markers associating with acute adverse effects following radiotherapy for several types of cancer patients},
 year = {2009}
}