@misc{oai:repo.qst.go.jp:00070511,
 author = {Imai, Takashi and Ishikawa, Atsuko and Suga, Tomo and Otsuka, Yoshimi and 今井 高志 and 石川 敦子 and 菅 智 and 荘司 好美},
 month = {Sep},
 note = {Caspase-7 (CASP7) is one of the effector caspases responsible for cleaving intracellular substrates involved in promoting the apoptotic phenotype. Interestingly a role for CASP7 in cell cycle progression at mitosis has also been suggested. Additionally, CASP7 polymorphisms are associated with increased risk for several types of cancer such as breast cancer, endometrial cancer and lung cancer. However little is known about the association of CASP7 with individual radiosensitivity. Therefore, in this study, we analyzed the association of functional polymorphisms in CASP7 with the risk of an adverse reaction in the intestinal tract after radiotherapy.
A total of 208 cervical cancer patients who had been treated with pelvic radiotherapy were genetically analyzed. Early gastrointestinal reactions were graded using the National Cancer Institute Common Toxicity Criteria, and patients were dichotomized into a lower-grade (LG) group (! Grade = 0 or 1, n = 150) and a higher-grade (HG) group (Grade = 2 or 3, n = 58). Three SNPs with minor allele frequencies of more than 5% in our healthy control samples, rs12415607 (C-1222A), rs11593766 (T398G, Asp4Glu), and rs2227310 (C1151G, Asp255Glu), were subjected to genotype and haplotype analyses in the cervical cancer patients.
Among these 3 SNPs, only rs11593766 was found to be associated with a risk of adverse reaction in the intestinal tract. The frequency of the G allele of this SNP was significantly higher in the HG group (18%) than in the LG group (9%; odds ratio [OR], 2.24; 95% confidence interval [CI], 1.18-4.21; P = 0.016). The GG and TG genotypes of rs11593766 were significantly associated with an increased risk of adverse reaction in the intestinal tract (OR, 2.15; 95% CI, 1.04-4.44; P = 0.038). No significant haplotype including rs11593766 was detected. Diplotypes of NPAT-ATM and AURKA have also been reported to con t! ribute to the risk of adverse intestinal reaction after radiotherapy, and we found that patients who had two or more of the NPAT-ATM, AURKA or CASP7 risk genotypes showed higher risk than other patients (OR, 3.60; 95% CI, 1.83-7.19; P = 0.00007).
Our results suggest that the rs11593766 GG and TG genotypes (Glu/Glu or Asp/Glu) of CASP7 might contribute to the individual risk of adverse intestinal reaction after radiotherapy., 14th International Congress of Radiation Research(ICRR’2011)},
 title = {Association of the caspase-7 Asp4Glu polymorphism with increased risk of adverse reaction in the gastrointestinal tract after pelvic radiotherapy in cervical cancer patients},
 year = {2011}
}