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Author Alam, Asim ♦ Mukhopadhyay, Nitai D. ♦ Ning, Yi ♦ Reshko, Leonid B. ♦ Cardnell, Robert J. G. ♦ Alam, Omair ♦ Rabender, Christopher S. ♦ Yakovlev, Vasily A. ♦ Walker, Linda ♦ Anscher, Mitchell S. ♦ Mikkelsen, Ross B.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword RADIOLOGY AND NUCLEAR MEDICINE ♦ ANIMAL TISSUES ♦ BIOLOGICAL REPAIR ♦ BLOOD ♦ COMPARATIVE EVALUATIONS ♦ DIAGNOSIS ♦ DNA ♦ FIBROSIS ♦ GENES ♦ HAZARDS ♦ HEAD ♦ HUMAN POPULATIONS ♦ INFLAMMATION ♦ MEDICAL PERSONNEL ♦ NECK ♦ NUCLEOTIDES ♦ PATIENTS ♦ RADIOTHERAPY ♦ TOXICITY ♦ WOUNDS
Abstract Purpose: This study tested whether racial differences in genetic polymorphisms of 4 genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiation therapy and indicate potential therapeutic targets. Methods and Materials: This prospective study examined genetic polymorphisms that modulate the expression of 4 genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3, and TGFβ1). DNA from blood samples of 179 patients (∼80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were as follows: 56% white, 43% African American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared with those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later after therapy, were also analyzed. Results: Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African American and white populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African Americans but not whites. A combined analysis of these polymorphisms revealed that >90% of African American patients with late effects had at least 1 of these minor alleles, and 58% had 2 or more. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. Conclusions: These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the possibility of such ethnic heterogeneity in the late toxicities of radiation.
ISSN 03603016
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-10-01
Publisher Place United States
Journal International Journal of Radiation Oncology, Biology and Physics
Volume Number 93
Issue Number 2


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