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S. Sharma



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    P2.06 - Epidemiology/Primary Prevention/Tobacco Control and Cessation (ID 707)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
    • Presentations: 1
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      P2.06-004 - Role of Polymorphic Variants of BER and DSBR Pathway Genes in Modulating Lung Cancer Susceptibility and Prognosis of North Indian Population (ID 8873)

      09:30 - 09:30  |  Author(s): S. Sharma

      • Abstract
      • Slides

      Background:
      DNA repair system uphold individuals’ genomic content from consistence impertinence implicated by continuous exposure to DNA damaging agents present in tobacco smoke, ionizing radiations,air pollution etc. BER (Base excision repair) and DSBR (Double strand break repair) are the two important pathways in this respect. However, polymorphic DNA repair genes might modulate the repair capacity and ultimately the survival.

      Method:
      Genotyping for the SNPs for genes OGG1, MUTYH, XRCC1, XRCC3, XRCC4, XRCC6, XRCC7.was done. Statistical analysis was done using MEDCALC. Logistic regression was used to evaluate the odds ratio. We even did use data mining tools MDR (Multi-dimensionality Reduction) and CART (Classification and regression tree analysis) to analyze the high interacting groups posing high risk. Survival analysis was done using Kaplan meier, and Cox regression analysis.

      Result:
      Statistical analysis revealed some interesting facts in relation to susceptibility. It was revealed that OGG1 Ser[326]Cys possessed a potent risk (OR=2.4, p= 0.0003) towards lung cancer whereas mutant genotype (GG) was protective towards lung cancer (OR=0.4, p=0.0185). Further analysis revealed XRCC1 Gln[632]Gln (OR=2.67, p=<0.001) depicted an overall high risk towards lung cancer. Histological analysis suggested mutant genotype in case of XRCC1 Pro[206]Pro implied a protective effect for SCLC subtype (OR=0.29, p=0.0017) on the contrary XRCC1 Gln[632]Gln showed a high risk in SQCC diseased group (OR=4.16, p=<0.0001). A high risk was observed on combining XRCC1 Gln[632]Gln with XRCC1 Pro[206]Pro (OR=5.6, p<0.0004) and Arg[194]Trp (OR=2.10, p=0.03). MDR analysis showed three factor model including XRCC1 206, 632, 280 was the best model (CVC=10, prediction error=0.34). Further Classification and Regression tree (CART) analysis revealed terminal node 1 carrying mutant of XRCC1 632 and wild type of XRCC1 280 represented the highest risk group. Further, survival analysis revealed a minor involvement of XRCC1 SNPs in survival. It was observed mutant genotype for XRCC1 Arg[399]Gln showed an insignificant better survival (MST=9.6). XRCC1 Gln[632]Gln showed a high hazards rate for SCLC subtype (H.R=0.26, p=0.05). An interesting finding of the study was related to chemotherapy regimen where Cisplatin/Carboplatin+ Docetaxel was observed to increase survival for XRCC1 399 mutant genotype (AA) (H.R=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; H.R=0.23, p=0.012).

      Conclusion:
      To conclude the polymorphic DNA repair genes affect the susceptibility in lung cancer patients of North Indian population. However, the prognosis is not much altered. The analysis of individualized chemotherapy would help us to develop prognostic biomarkers for individualized therapy.

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