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Genetic Investigation of Polymorphic OGG1 and MUTYH Genes Towards Increased Susceptibility in Lung Adenocarcinoma and its Impact on Overall Survival of Lung Cancer Patients Treated with Platinum Based Chemotherapy

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Pathology & Oncology Research

Abstract

Genes OGG1 and MUTYH are the two primary genes in Base excision repair pathway. OGG1 hydrolyzes the sugar phosphate backbone and remove the damaged base creating abasic site. MUTYH complements OGG1 as it particularly remove adenine mispaired with 8-oxo-G. Both OGG1 and MUTYH act as a check for the mis-incorporation of bases may be due to damages incurred on DNA. DNA isolation for 326 lung cancer cases and 330 controls was followed by genotyping making use of PCR-RFLP. Logistic regression was done to analyze the risk towards lung cancer. Patients were followed through telephonic conversation. Kaplan meier and Cox-regression were used for survival analysis. OGG1 presented a high risk towards lung cancer (CG: OR = 2.44, p = 0.0003; CG + GG: OR = 1.88, p = 0.0093). On the same lines adenocarcinoma for OGG1 were potent risk factors towards lung cancer (CG: OR = 4.72, p = 0.0002; CG + GG: OR = 3.63, p = 0.0018). Single allelic carriers for MUTYH gene imposed a high risk towards overall lung susceptibility and for all the three histology. Stratified analysis for chemotherapeutic drugs revealed administration of Cisplatin/Carboplatin + Pemtrexed for OGG1Ser 326 Cys showed a better survival (MST CG vs. CC: 9.1 vs. 0.56, p = <0.0001; HR =0.051, p = 0.0025). Whereas, MUTYH Gln324His showed a smaller survival for mutant genotype (CC) (MST CC vs. GG: 4.0 vs. 9.4, p = 0.05; HR = 1.75, p = 0.26). Single allelic carriers for both OGG1 and MUTYH were risk factors towards lung cancer. The risk was amplified on combining both OGG1 and MUTYH.

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Acknowledgments

We would like to express our gratitude to all the subjects who participated in this current study. This work was supported by grant from the Indian Council of Medical Research, New Delhi, India (Grant No. 5/13/126/2011/NCD-III).

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Authors and Affiliations

  1. Department of Biotechnology, Thapar University, Patiala, Punjab, 147002, India

    Amrita Singh & Siddharth Sharma

  2. Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 14, Chandigarh, India

    Navneet Singh & Digambar Behera

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  1. Amrita Singh
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Correspondence to Siddharth Sharma.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Singh, A., Singh, N., Behera, D. et al. Genetic Investigation of Polymorphic OGG1 and MUTYH Genes Towards Increased Susceptibility in Lung Adenocarcinoma and its Impact on Overall Survival of Lung Cancer Patients Treated with Platinum Based Chemotherapy. Pathol. Oncol. Res. 25, 1327–1340 (2019). https://doi.org/10.1007/s12253-017-0372-6

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