Association of DNA Repair and Steroid Metabolism Gene Polymorphisms with Clinical Late Toxicity in Patients Treated with Conformal Radiotherapy for Prostate Cancer

Damaraju, Sambasivarao; Murray, David; Dufour, Jennifer; Carandang, Diana; Myrehaug, Sten; Fallone, B. G.; Field, Colin; Greiner, Russell; Hanson, John; Cass, Carol E.; Parliament, Matthew

doi:10.1158/1078-0432.ccr-05-2703

Cited by 131 publications

(95 citation statements)

References 59 publications

(59 reference statements)

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“…Some of these genes belong to the cellular pathways responsible for the repair of DNA damage after ionizing radiation exposure: the base excision repair (hOGG1 and XRCC1) and the double-strand breaks repair (XRCC3). 36,37 In contrast, ERCC1 gene, included in the nucleotide excision repair pathway, is mostly involved in the repair of bulky DNA adducts associated with the action of platinum derivatives. [38][39][40] Nonetheless, recent data highlighted that genetic polymorphisms of ERCC1 and of nucleotide excision repair pathway in general have an effect also on the therapeutic efficacy of RT.…”

Section: Discussionmentioning

confidence: 99%

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

et al. 2010

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The aim of the study was the identification of a pharmacogenetic profile predictive of the tumor regression grade (TRG), considered as tumor response parameter, after neo-adjuvant treatment in rectal cancer patients. A total of 238 rectal cancer patients treated in a neo-adjuvant setting by a fluoropyrimidines-based chemo-radiotherapy (RT) were genotyped for 25 genetic polymorphisms in 16 genes relevant for treatment-associated pathways. Two polymorphisms were associated with TRG in a multivariate analysis: hOGG1-1245C4G, which can affect radiosensitivity and MTHFR-677C4T, which is involved in fluoropyrimidines action. Patients bearing at least one variant allele had a lower chance to get TRGp2 (OR ¼ 0.46 95% CI 0.23-0.90, P ¼ 0.024; and OR ¼ 0.48 95% CI 0.24-0.96, P ¼ 0.034; respectively). An association trend was observed for ABCB1-3435C4T, which is responsible for the multi-drug resistance (odds ratio (OR) ¼ 1.96, 95% confidence interval (CI) 0.98-3.95, P ¼ 0.057). Exploratory classification and regression tree (CART) analysis highlighted high-order gene-gene and gene-environment interactions and a genetic signature associated with differential response, with hOGG1-1245C4G as the most predictive factor. Other significant variables were: ABCB1-3435C4T, MTHFR-677C4T, ERCC1-8092C4A, ABCC2-1249G4A, XRCC1-28152G4A, XRCC3-4541A4G and patients gender. On the basis of CART results, patients were categorized into three groups according to tumor response probability: intermediate and high profiles had a higher probability to get TRGp2 as compared with low profiles (OR ¼ 4.12 95% CI 1. Po0.001 and OR ¼ 12.44, Po0.0001, respectively). This study evidences a major role of hOGG1-1245C4G and MTHFR-677C4T polymorphisms in the tumor response of rectal cancer patients treated with chemo-RT in neo-adjuvant setting, and shows the relevance of gene-gene and gene-environment interactions for complex phenotypes as tumor response.

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Section: Discussionmentioning

confidence: 99%

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

et al. 2010

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“…Since different patients may present with different degrees of skin fibrosis despite receiving identical treatment, it was hypothesized that the severity of such complications may be genetically determined. Previous studies investigated the association of single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair, such as X-ray repair cross-complementing protein 1 (XRCC1) rs25487 (c.1196A>G, p.Gln399Arg) and X-ray repair cross-complementing protein 3 (XRCC3) rs861539 (c.722C>T, p.Thr241Met) with late complications in various types of cancer (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Association of XRCC1 and XRCC3 gene haplotypes with the development of radiation-induced fibrosis in patients with nasopharyngeal carcinoma

Cheuk

Yip

Kwong

et al. 2014

Molecular and Clinical Oncology

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Abstract. Radiation-induced fibrosis is one of the late complications of radiotherapy (RT) for nasopharyngeal carcinoma (NPC). The aim of this study was to investigate the association between X-ray repair cross-complementing protein 1 and 3 (XRCC1 and XRCC3, respectively) gene haplotypes and radiation-induced fibrosis in NPC patients. Genomic DNA was extracted from blood samples of 120 NPC patients previously treated with RT. In total, 12 tag single-nucleotide polymorphisms (SNPs) were selected from the XRCC1 and XRCC3 genes and were genotyped using restriction fragment length polymorphism analysis or unlabeled probe melting analysis. Single-marker and haplotype analyses were performed using multivariate logistic regression analysis. The functional variant rs861539 of XRCC3 may be associated with radiation-induced fibrosis [asymptotic P-value (P asym )<0.05]. No significant association was observed between radiation-induced fibrosis and any of the tag SNPs of XRCC1 and XRCC3 in either single-marker or haplotype analysis after 10,000 permutations [empirical P-value (P emp )>0.05]. Our preliminary results indicated that the rs861539 variant of XRCC3 may be associated with an increased risk of radiation-induced fibrosis; however, a large-scale study is required to confirm this result.

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“…Andreassen et al found a significant association between hetero-or homozygous carriership of 5557G>A and the development of subcutaneous fibrosis after radiotherapy [8]. A study of Damaraju et al [9], which included 83 patients treated with radiotherapy for localized prostate cancer, investigated the association between SNPs of several candidate genes. They found an association between 5557G>A and the development of late radiotherapy toxicity.…”

Section: Discussionmentioning

confidence: 99%

ATM and TGFB1 genes polymorphisms in prediction of late complications of chemoradiotherapy in patients with locally advanced cervical cancer

Paulíková¹,

Petera²,

Sirák³

et al. 2014

neo

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The purpose of our study was to evaluate a possible correlation between genetic polymorphisms in ATM and TGFB1 genes and late toxicity of chemoradiotherapy for locally advanced cervical cancer. Fifty five patients with FIGO stage IIB and higher without a disease recurrence with a mean follow up of 6 years were included. Late toxicity was assessed by EORTC/RTOG late toxicity criteria. Univariate and multivariate logistic regression model was used for statistical analysis. Degree of association between polymorphisms and late toxicity of chemotherapy was assessed on the basis of phi-coefficient (φ) as well. We did not find any association between 5557G>A polymorphism in the ATM gene or single TGFB1 polymorphisms and late toxicity. TGFB1 compound homozygosity (-1552delAGG, -509C>T, L10P) was a significant predictive factor of grade III-IV and any grade of complications in both univariate and multivariate logistic regression analyses and statistical significance of association between polymorphisms and late toxicity of chemoradiotherapy was confirmed also by the evaluation of phi-coefficient (φ). We conclude that haplotypes instead of single nucleotide polymorphic sites in the genes may better characterize the individual radiosensitivity.

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Association of DNA Repair and Steroid Metabolism Gene Polymorphisms with Clinical Late Toxicity in Patients Treated with Conformal Radiotherapy for Prostate Cancer

Abstract: Objective: To explore the possible relationship between single nucleotide polymorphisms (SNP)

Cited by 131 publications

References 59 publications

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

Association of XRCC1 and XRCC3 gene haplotypes with the development of radiation-induced fibrosis in patients with nasopharyngeal carcinoma

ATM and TGFB1 genes polymorphisms in prediction of late complications of chemoradiotherapy in patients with locally advanced cervical cancer

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