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Polymorphism in XRCC1 gene modulates survival and clinical outcomes of advanced North Indian lung cancer patients treated with platinum-based doublet chemotherapy

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Abstract

Survival in lung cancer patients is genetically determined. Single nucleotide polymorphisms (SNPs) in DNA repair genes are observed to play a critical role in survival as DNA repair itself can behave as double-edged sword. We aim to explore the association of DNA repair gene XRCC1 in survival and clinical outcomes for North Indian population. Blood sample from patients diagnosed with lung cancer was taken. DNA isolation and genotyping were performed for the SNPs of XRCC1 gene. Further, patients were followed up through telephonic conversation after every 2 months for 3 years. Statistical analysis was carried out using Kaplan–Meier to determine the median survival time (MST) and Cox proportional regression model to determine the hazards ratio. Further, logistic regression was used to calculate to calculate the objective response. The mutant genotype for XRCC1 399 is observed to have a better survival (MST = 9.6). Histological stratification did not reveal any association for any SNP except for SCLC subtype in XRCC1 632 with an increased death rate (HR 3.08, p = 0.02). On stratification according to chemotherapy regimen administered; cisplatin/carboplatin + docetaxel was observed to increase survival for XRCC1 399 mutant genotype (AA) (HR 0.26, p = 0.05). Cisplatin/carboplatin + irinotecan increased survival in both heterozygotes (GA) and combined variants (GA + AA) (HR 0.22, p = 0.014; HR 0.23, p = 0.012). The polymorphic variants within the XRCC1 gene have found to play an important role in overall survival of lung cancer patients undergoing specific chemotherapy regimen.

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Abbreviations

LC:

Lung cancer

SQCC:

Squamous cell carcinoma

ADCC:

Adenocarcinoma

SCLC:

Small cell lung carcinoma

NSCLC:

Non-small cell lung carcinoma

DRC:

DNA repair capacity

OS:

Overall survival

ECOG:

Eastern cooperative oncology group

KPS:

Karnofsky’s response status

RECIST:

Response evaluation criteria in solid tumors

CR:

Complete response

PR:

Partial response

SD:

Stable disease

PD:

Progression disease

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Acknowledgements

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 Education and Medical 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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Singh, A., Singh, N., Behera, D. et al. Polymorphism in XRCC1 gene modulates survival and clinical outcomes of advanced North Indian lung cancer patients treated with platinum-based doublet chemotherapy. Med Oncol 34, 64 (2017). https://doi.org/10.1007/s12032-017-0923-4

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