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XPC Polymorphism and Risk for Lung Cancer in North Indian Patients Treated with Platinum Based Chemotherapy and Its Association with Clinical Outcomes

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

Xeroderma pigmentosum complementation group C plays an important role in the human repair system. As reported in previous studies its polymorphism are associated with lung cancer susceptibility. The purpose of this study is to investigate the association of XPC gene with lung cancer susceptibility, overall response and clinical outcomes amongst North Indians. A hospital based study of 370 lung cancer cases and 370 healthy controls was conducted and genotypes were determined using PCR-RFLP assay. Results were assessed using logistic linear regression adjusted for age, sex and smoking status. Survival analysis was conducted using Kaplan-Meier survival analysis and Cox regression analysis. The treatment outcomes of 167 lung cancer patients treated with platinum based chemotherapy were evaluated.The mutant genotypic variant of XPC Lys939Gln has been associated with elevated risk of lung cancer(OR:2.30;95%CI:1.41-3.73;p=0.0007) whereas XPC Ala499Val showed a highly protective effect (OR:0.25;95%CI:0.10-0.63;p=0.003). The mutant genotype of XPC Lys939Gln presented a higher risk of developing lung cancer in heavy smokers (OR: 3.71; 95%CI:1.46-9.45; p=0.005). The survival analysis presented that heterozygous genotype showed least survival in comparison with mutant genotype in XPC Ala499Val genetic variant whereas no significant association was observed in XPC Lys939Gln. In conclusion, XPC Lys939Gln is associated with significant risk towards the lung cancer whereas on contrary XPC Ala499Val shows a protective effect.

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Abbreviations

ADCC:

(Adenocarcinoma)

HR:

(Hazard ratio)

MST:

(Mean survival time)

ns SNPs:

(Non synonymous single nucleotide polymorphism)

OR:

(Odds ratio)

SCLC:

(Small cell lung cancer)

SQCC:

(Squamous cell carcinoma)

XPC:

(Xeroderma pigmentosum group C)

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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, Punjab, 147002, India

    Shweta Lawania & Siddharth Sharma

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

    Navneet Singh & Digamber Behera

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  1. Shweta Lawania
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Correspondence to Siddharth Sharma.

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Lawania, S., Singh, N., Behera, D. et al. XPC Polymorphism and Risk for Lung Cancer in North Indian Patients Treated with Platinum Based Chemotherapy and Its Association with Clinical Outcomes. Pathol. Oncol. Res. 24, 353–366 (2018). https://doi.org/10.1007/s12253-017-0252-0

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