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A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGF?1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity.

ABSTRACT: 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.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 TGF?1). 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.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 TGF?1 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.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.

SUBMITTER: Alam A

PROVIDER: S-EPMC4575610 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity.

Alam Asim A Mukhopadhyay Nitai D ND Ning Yi Y Reshko Leonid B LB Cardnell Robert J G RJ Alam Omair O Rabender Christopher S CS Yakovlev Vasily A VA Walker Linda L Anscher Mitchell S MS Mikkelsen Ross B RB

International journal of radiation oncology, biology, physics 20150606 2

<h4>Purpose</h4>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.<h4>Methods and materials</h4>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) ...[more]

PMID: 26238954

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Project description:PurposeX-Ray Repair Cross Complementing 1 (XRCC1) functioning in the base excision repair pathway plays an important role in the repair of DNA single-strand breaks caused by ionizing radiation. The relationship between XRCC1 polymorphisms and the risk of radiation-induced side effects on normal tissues remains controversial. Therefore, we performed a comprehensive meta-analysis to elucidate these associations.Materials and methodsA systematic literature search was carried out in PubMed, Medline (Ovid), Embase, Web of Science, Cochrane database, and the references of relevant studies. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association.ResultsA total of 40 studies including 6,682 patients were eventually identified in this meta-analysis. Pooled results suggested that rs25487 Arg399Gln polymorphism significantly increased the risk of acute radiation-induced side effects (OR=1.29, 95% CI: 1.10-1.52, P=0.002), especially acute mucositis (OR=1.91, 95% CI: 1.17-3.11, P=0.01) and acute gastrointestinal and genitourinary toxicity (OR=1.49, 95% CI: 1.04-2.11, P=0.03). Furthermore, patients who received head and neck irradiation with rs25487 Arg399Gln polymorphism were more likely to experience radiotherapy (RT)-induced side effects (OR=1.46, 95% CI: 1.12-1.90, P=0.005). However, no statistically significant correlations were identified between rs25487 polymorphism and any late side effects and other irradiation areas. Likewise, no significant associations were detected between rs25489, rs1799782, or rs3213245 polymorphism and RT-induced toxicity.ConclusionOur meta-analysis demonstrated that XRCC1 rs25487 Arg399Gln polymorphism had a significant predictive value and might predict a risk of severely acute RT-induced adverse effects, especially in acute mucositis and acute gastrointestinal and genitourinary toxicity, or in patients with head and neck irradiation. However, large-scale and well-designed studies are required to further evaluate the predictive value of XRCC1 variations on radiation-induced side effects in order to identify radiosensitive patients and predict radiotoxicity.

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Dataset Information

A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGF?1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity.

Publications

A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity.

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