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DNA Base-Excision Repair Genes OGG1 and NTH1 in Brazilian Lung Cancer Patients

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Abstract

Introduction

Lung cancer is the leading global cause of cancer-related mortality and is associated with poor prognosis. To improve survival rates of lung cancer patients, better understanding of tumorigenic mechanisms is necessary, which may lead to development of new therapeutic strategies. The hOGG1 and NTH1 genes act in the DNA BER repair pathway and their involvement in lung cancer pathogenesis has been analyzed in several populations.

Methods

We analyzed targeted regions of the hOGG1 and NTH1 genes in 96 Brazilian patients with non-small-cell lung cancer (NSCLC) and 89 cancer-free, ethnically matched controls.

Results

The NTH1 c.98G>T polymorphism rs2302172 (p = 0.02 and p = 0.02 for allele and genotype frequency between cases and controls, respectively) and the 140-17C> T variant (rs2233518) (p = 0.02 and p = 0.02 for allele and genotype frequency between cases and controls, respectively) were detected in four lung cancer cases (4 %) while the NTH1 Q131K (C391A) polymorphism was found in seven lung cancer cases (7 %) (p = 0.001 and p = 0.008, for allele and genotype frequency between cases and controls, respectively). None of these sequence variants were detected in controls. The Ser326Cys (C1245G, rs1052133) polymorphism in the OGG1 gene was detected in 42 % of analyzed NSCLC patients and in 34 % of the controls (p = 0.11 and p = 0.25 for allele and genotype frequency between cases and controls, respectively).

Conclusions

Our study provides preliminary evidence that polymorphisms in OGG1 do not contribute to development of NSCLC in Brazilian patients and that NTH1 polymorphisms may be associated with NSCLC pathogenesis.

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Acknowledgments

We are grateful to all patients.

Author contributions

Drs. L. De Marco, E. Friedman and M. A. Bicalho designed the study and applied for Research Ethics Board approval. Drs. A. J. Bicalho, F. B. Leidenz, M. A. Bicalho, L. Bastos-Rodrigues and Mrs. P. G. Couto recruited the patients and collected the data. Drs. L. Bastos-Rodrigues and Mrs. P. G. Couto analyzed the data and prepared draft figures and tables. Mrs. P. G. Couto prepared the manuscript draft with important intellectual input from Drs. L. De Marco and E. Friedman. All authors approved the final manuscript.

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Authors and Affiliations

  1. Department of Surgery, Universidade Federal de Minas Gerais, Av. Alfredo Balena 190, Room 114, Belo Horizonte, 30130-100, Brazil

    Patricia G. Couto, Fernanda Guieiro, Franciele B. Leidenz, Ana J. Bicalho & Luiz De Marco

  2. Universidade Federal de Juiz de Fora, Campus Governador Valadares, Governador Valadares, Minas Gerais, Brazil

    Luciana Bastos-Rodrigues

  3. Faculty of Medical Science, Centro de Ensino Superior e Desenvolvimento, Campina Grande, Brazil

    Juliana G. Carneiro

  4. Department of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Maria Aparecida Bicalho

  5. The Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Eitan Friedman

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  1. Patricia G. Couto
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Corresponding author

Correspondence to Luiz De Marco.

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Conflict of interest

The authors declare that there are no conflicts of interest.

Funding

This work was partially funded to L. De Marco by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq # 405053/2013-4) and Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG # APQ-00220-14), Brazil.

Ethical approval and informed consent

The Ethics Committee of Universidade Federal de Minas Gerais approved this study (ETIC 473-05). All subjects signed an informed consent.

The manuscript does not contain clinical studies or patient data and followed the Declaration of Helsinki guidelines.

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Couto, P.G., Bastos-Rodrigues, L., Carneiro, J.G. et al. DNA Base-Excision Repair Genes OGG1 and NTH1 in Brazilian Lung Cancer Patients. Mol Diagn Ther 19, 389–395 (2015). https://doi.org/10.1007/s40291-015-0164-1

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  • DOI: https://doi.org/10.1007/s40291-015-0164-1

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