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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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.
KeywordsLung cancer Single nucleotide polymorphism XRCC1 Overall survival Hazards rate Chemotherapy
Squamous cell carcinoma
Small cell lung carcinoma
Non-small cell lung carcinoma
DNA repair capacity
Eastern cooperative oncology group
Karnofsky’s response status
Response evaluation criteria in solid tumors
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).
Compliance with ethical standards
Conflict of interest
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 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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