Role of polymorphic variants of BER and DSBR pathway genes in modulating lung cancer susceptibility and prognosis of North Indian Population Amrita Singh, Navneet Singh, D. Behera and Siddharth Sharma Department of Biotechnology, Thapar University Department of Pulmonary Medicine, PGIMER Chandigarh
Results
Objective To investigate the influence of DNA repair genes i.e. BER genes and DSBR pathway genes towards lung cancer and survival of Lung cancer patients in North Indian Population when they are treated with Platinum based doublet Chemotherapy.
Introduction DNA repair system upholds the integrity of genomic content of the body. BER(Base excision repair pathway)and DSBR (Double Strand Break repair pathway)are two important repair pathways that repair single base damages and double strand damages respectively. Polymorphic DNA repair genes over the time pave way for susceptibility towards Lung cancer and modulate survival after Platinum based doublet Chemotherapy.
Figure: Demography
Figure: Histology
Acknowledgements The author thanks the Indian Council of Medical Research (ICMR) for funding this research through grant and also thanks Post Graduate Institute of Medical Education and Research (PGIMER) Chandigarh for samples and support.
Contact Information • Email:
[email protected] • Phone: +91 (872) 882 9637
Table 1 showcase the association of polymorphic variants of DNA Repair pathways with Lung cancer. Adjusted odds ratio shows XRCC1 632 acts as a potent risk factor towards Lung cancer. Single allelic carriers in case of OGG1 326 and MUTYH 324 shows a high risk towards Lung cancer. The polymorphic variants of DSBR genes XRCC6 and XRCC7 did not show any association with Lung cancer. Survival analysis done for the same genes did not show any significant influence on survival for the same polymorphic genes. Haplotype analysis (Table 2) was performed for the five polymorphic variants of XRCC1. Results indicated that Haplotype block 5 with wild type genotype for XRCC1 206 showed the highest risk towards Lung cancer. Whereas Haplotype block 4 with mutant allele for XRCC1 399 depicted a high protective effect towards Lung cancer. Table: Haplotype analysis of five XRCC1 SNPs
Material and Method A total of 350 Lung cancer patients and healthy controls were genotyped for the study using PCR-RFLP method. The statistical analysis was performed using Logistic Regression to evaluate the Adjusted odds ratio. Median survival time and Hazard rate using Univariate and Multivariate analysis respectively.
Figure: The multifactor dimensionality reduction (MDR) interaction Dendrogram
Results
Figure: Smoking
Table: DNA repair genes and their association with Lung Cancer
Genes Controls XRCC1 399 G/A GG 79(24.3) GA 176(54.1) AA 70(21.5) XRCC1 194 C/T CC 267(82.1) CT 55(16.9) TT 3(0.92) XRCC1 632 G/A GG 124(38.1) GA 127(39.0) AA 74(22.7) XRCC1 280 G/A GG 26(8.0) GA 268(82.4) AA 31(9.5) OGG1 326 C/G CC 60(18.1) CG 189(57.2) GG 81(24.5) MUTYH 324 G/C GG 227(68.7) GC 90(27.2) CC 13(3.9)
Cases
AOR (95 C.I.)
93(28.1) 1.0(Reference) 186(56.3) 0.88(0.60-1.28) 51(15.4) 0.61(0.37-1.0) 256(77.5) 1.0(Reference) 72(21.8) 1.29(0.86-1.95) 2(0.60) 0.50(0.075-3.38)
p
0.50 0.06
0.20 0.48
61(18.4) 1.0(Reference) 142(43.0) 2.2(1.427-3.29) 127(38.4) 3.4(2.26-5.39)
0.0001
