DNA Damage and Repair Capacity in Patients With Lung Cancer: Prediction of Multiple Primary Tumors

PurposePatients who survive one occurrence of non–small-cell lung cancer (NSCLC) are at higher risk of a second malignancy. Capacity to repair damaged DNA may modulate individual susceptibility to develop lung cancer. Therefore, we evaluated constitutive and induced DNA damage, and repair capacity, in patients with multiple NSCLCs (cases) and compared the results to those obtained in patients with a single NSCLC (controls).Patients and MethodsOne hundred eight cases and 99 controls matched by age, sex, and time since diagnosis were studied. DNA damage was assessed on peripheral blood lymphocytes by the comet assay before and after exposing cells to a tobacco-derived carcinogen, using the tail moment and the tail intensity as measures to assess baseline damage, induced damage and repair capacity.ResultsConstitutive DNA damage, benzo(a)pyrene diol epoxide–induced damage, and repair after BPDE-induced damage were all significantly higher in cases than in controls. These results were confirmed in regression analyses adjusted for potential confounders.ConclusionDNA damage as measured by the comet assay is associated with the development of multiple primary tumors in individuals with NSCLC.

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DNA damage and repair capacity by comet assay in lymphocytes of white-collar active smokers and passive smokers (non- and ex-smokers) at workplace

Toxicology Letters ◽

10.1016/j.toxlet.2006.09.003 ◽

2006 ◽

Vol 167 (2) ◽

pp. 131-141 ◽

Cited By ~ 43

Author(s):

Maria Enrica Fracasso ◽

Denise Doria ◽

Paola Franceschetti ◽

Luigi Perbellini ◽

Luciano Romeo

Keyword(s):

Dna Damage ◽

Comet Assay ◽

White Collar ◽

Repair Capacity ◽

Dna Damage And Repair

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Expression of critical genes used as prognostic biomarkers and DNA damage in lymphocytes from breast cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10641 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10641-10641 ◽

Cited By ~ 1

Author(s):

F. Franke ◽

M. Agnoletto ◽

J. Saffi ◽

T. Guecheva

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Dna Repair ◽

Comet Assay ◽

Cancer Patients ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Breast Cancer Patients ◽

Dna Damage And Repair ◽

Blood Lymphocytes

10641 Breast cancer is the most common malignancy among women and its rate of mortality is still high. The increase knowledge of breast cancer biology is heaving great impact on determining the clinical prognosis and response to treatment. Impaired DNA repair may elevate the risk of malignant transformation of breast cells due to the accumulation of spontaneous mutations in target genes and increasing susceptibility to exogenous carcinogens. The present study was designed to evaluate the relationship between DNA damage and expression of some critical genes including TP53, c-ERBB2, ER (Estrogen Receptor) and PR (Progesterone Receptor) in breast cancer. Blood samples were obtained from female patients with diagnosed breast cancer before chemotherapy as well as from healthy individuals, and were processed in 24 hours. To evaluate the role of DNA repair in breast cancer we determined the level of DNA damage and the capacity to remove DNA damage induced by hydrogen peroxide in the peripheral blood lymphocytes. For this purpose the alkaline version of the comet assay, which provides a sensitive tool to investigate DNA damage and repair, was applied. The level of basal DNA damage was higher in breast cancer patients compared to the control group. Considerable inter-individual variations of DNA damage and repair in breast cancer patients were observed both before and after the treatment. The correlation between DNA damage in peripheral blood and expression of p53, c-erbB-2, PR and ER was analyzed. This preliminary study indicates that the DNA damage accumulation, observed in peripheral blood lymphocytes of breast cancer patients in early stages, could be attributed to impaired DNA repair. Our results suggest that DNA damage, as evaluated by the comet assay, seems to be useful molecular biomarker for monitoring ongoing exposures to DNA damaging agents. Such a research on the mutagen sensitivity and efficacy of DNA repair could impact on the development of new diagnostic and screening strategies. Work Supported by FAPERGS and GENOTOX (UFRGS). No significant financial relationships to disclose.

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Measurement of DNA Damage and Repair Capacity as a Function of Age Using the Comet Assay

Aging Methods and Protocols ◽

10.1385/1-59259-070-5:143 ◽

2003 ◽

pp. 143-157 ◽

Cited By ~ 3

Author(s):

Peter H. Clingen ◽

Jillian E. Lowe ◽

Michael H. L. Green

Keyword(s):

Dna Damage ◽

Comet Assay ◽

Repair Capacity ◽

Dna Damage And Repair

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Primary DNA Damage Assessed With the Comet Assay and Comparison to the Absorbed Dose of Diagnostic X-rays in Children

International Journal of Toxicology ◽

10.1177/1091581809344775 ◽

2009 ◽

Vol 28 (5) ◽

pp. 405-416 ◽

Cited By ~ 10

Author(s):

Đurđica Milković ◽

Vera Garaj-Vrhovac ◽

Mária Ranogajec-Komor ◽

Saveta Miljanić ◽

Goran Gajski ◽

...

Keyword(s):

Dna Damage ◽

Comet Assay ◽

Absorbed Dose ◽

Peripheral Blood Lymphocytes ◽

X Rays ◽

X Ray ◽

Before And After ◽

The Individual ◽

Dose Measurements ◽

Posterior Anterior

The aim of this work is to assess DNA damage in peripheral blood lymphocytes of children prior to and following airway X-ray examinations of the chest using the alkaline comet assay and to compare data with the measured absorbed dose. Twenty children with pulmonary diseases, between the ages of 5 and 14 years, are assessed. Absorbed dose measurements are conducted for posterior–anterior projection on the forehead, thyroid gland, gonads, chest, and back. Doses are measured using thermoluminescent and radiophotoluminescent dosimetry systems. Differences between tail lengths, tail intensity, and tail moments as well as for the long-tailed nuclei before and after exposures are statistically significant and are dependent on the individual. The results demonstrate the usefulness of the comet assay as a measure of X-ray damage to lymphocytes in a clinical setting. Doses measured with both dosimeters show satisfactory agreement (0.01 mSv) and are suitable for dosimetric measurements in X-ray diagnostics.

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O-054 Genetic instability, response to DNA damage, and repair capacity in individuals with multiple primary non-small cell lung cancers

Lung Cancer ◽

10.1016/s0169-5002(05)80186-2 ◽

2005 ◽

Vol 49 ◽

pp. S21

Author(s):

I. Orlow ◽

B. Park ◽

B. Clas ◽

U. Mujumdar ◽

G. Dominguez ◽

...

Keyword(s):

Dna Damage ◽

Genetic Instability ◽

Small Cell ◽

Small Cell Lung ◽

Repair Capacity ◽

Dna Damage And Repair ◽

Lung Cancers ◽

Multiple Primary

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DNA crosslinks, DNA damage and repair in peripheral blood lymphocytes of non-small cell lung cancer patients treated with platinum derivatives

Oncology Reports ◽

10.3892/or.2013.2805 ◽

2013 ◽

Vol 31 (1) ◽

pp. 391-396 ◽

Cited By ~ 11

Author(s):

PETRA FIKROVA ◽

RUDOLF STETINA ◽

MICHAL HRNCIARIK ◽

DANA HRNCIARIKOVA ◽

MILOSLAV HRONEK ◽

...

Keyword(s):

Lung Cancer ◽

Dna Damage ◽

Cancer Patients ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Small Cell ◽

Small Cell Lung ◽

Dna Damage And Repair ◽

Lung Cancer Patients ◽

Dna Crosslinks

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Cross-Linking Interferes with Assessing Sulfur Mustard-Induced DNA Damage in Human Peripheral Blood Lymphocytes Using the Comet Assay

Toxicology Mechanisms and Methods ◽

10.1080/15376520490429120 ◽

2004 ◽

Vol 14 (3) ◽

pp. 195-202 ◽

Cited By ~ 7

Author(s):

Janet Moser ◽

Claire F. Levine ◽

Delvena R. Thomas-Dunmeyer ◽

William J. Smith

Keyword(s):

Dna Damage ◽

Comet Assay ◽

Peripheral Blood ◽

Sulfur Mustard ◽

Human Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Cross Linking ◽

Blood Lymphocytes ◽

Human Peripheral Blood Lymphocytes

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Multiple Primary Tumors in a Family with Li-Fraumeni Syndrome with a TP53 Germline Mutation Identified by Next-Generation Sequencing

The International Journal of Biological Markers ◽

10.5301/jbm.5000227 ◽

2016 ◽

Vol 31 (4) ◽

pp. 461-465 ◽

Cited By ~ 2

Author(s):

Valentina Zampiga ◽

Rita Danesi ◽

Gianluca Tedaldi ◽

Michela Tebaldi ◽

Ilaria Cangini ◽

...

Keyword(s):

Next Generation Sequencing ◽

Genetic Analysis ◽

Germline Mutation ◽

Tp53 Mutation ◽

Primary Tumors ◽

Li Fraumeni Syndrome ◽

Multiple Primary Tumors ◽

Targeted Ngs ◽

Multiple Primary ◽

Generation Sequencing

Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder occurring at a young age that predisposes individuals to multiple forms of cancer and to a heterogeneous spectrum of malignancies. We describe the clinical history of a patient who had 5 primary malignant cancers and a familiar history consistent with LFS. We analyzed the genomic DNA of the proband and her relatives by next-generation sequencing (NGS) technology using an enrichment protocol for the simultaneous sequencing of 94 genes involved in hereditary cancers. Genetic analysis of the proband revealed a TP53 germline mutation in exon 5 determining a nucleotide alteration at codon 175 (R175H), a hot spot mutation site related to LFS and a reported pathogenic mutation. The proband daughter's and brother's DNA did not carry the TP53 mutation but they had some rare variants in common with the proband, in addition to other variants with a still unclear role. In conclusion, we identified a TP53 mutation in a patient with multiple primary tumors and a family history characterized by a severe susceptibility to cancer. The genetic analysis by targeted NGS led to the identification of the genetic background and to the exclusion of a cancer risk for the family members. Targeted NGS represents an efficient approach for the identification of mutations in families with a heterogeneous phenotype.

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