title: A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Asim
authors.initials: A
authors.lastname: Alam
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Nitai D
authors.initials: ND
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Family Medicine and Population Health, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Leonid B
authors.initials: LB
authors.lastname: Reshko
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Robert J G
authors.initials: RJ
authors.lastname: Cardnell
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Omair
authors.initials: O
authors.lastname: Alam
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Rabender
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Vasily A
authors.initials: VA
authors.lastname: Yakovlev
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Linda
authors.initials: L
authors.lastname: Walker
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Anscher
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia. Electronic address: rmikkels@vcu.edu.
authors.forename: Ross B
authors.initials: RB
authors.lastname: Mikkelsen
mesh_terms: D001741:Black or African American / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D001943:Breast Neoplasms / Q000208:ethnology / Q000532:radiotherapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000208:ethnology / Q000532:radiotherapy; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000532:radiotherapy; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000532:radiotherapy; D011832:Radiation Injuries / Q000208:ethnology / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D044465:White People / Q000235:genetics*; D014945:Wound Healing / Q000235:genetics*
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1