Jing Jin1, Heather Robeson1, Pebbles Fagan2,3,4, Mohammed S Orloff1,3,4. 1. Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America. 2. Department of Health Behavior and Health Education, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America. 3. Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America. 4. Center for the Studies of Tobacco, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Abstract
OBJECTIVE: The carcinogenesis role of PARP1 in lung cancer is still not clear. Analysis at allelic levels cannot fully explain the function of PARP1 on lung cancer. Our study aims to further explore the relation between PARP1 haplotypes and lung cancer. MATERIALS AND METHODS: DNA and RNA were extracted from non-small cell lung cancer (NSCLC) tumor and adjacent normal fresh frozen tissue. Five PARP1-SNPs were genotyped and PARP1-specific SNPs were imputed using IMPUTE and SHAPEIT software. The SNPs were subjected to allelic, haplotype and SNP-SNP interaction analyses. Correlation between SNPs and mRNA/protein expressions were performed. RESULTS: SNP imputation inferred the ungenotyped SNPs and increased the power for association analysis. Tumor tissue samples are more likely to carry rs1805414 (OR = 1.85; 95% CI: 1.12-3.06; P-value: 0.017) and rs1805404 (OR = 2.74; 95%CI 1.19-6.32; P-value: 0.015) compared to normal tissues. Our study is the first study to show that haplotypes comprising of 5 SNPs on PARP1 (rs1136410, rs3219073, rs1805414, rs1805404, rs1805415) is able to differentiate the NSCLC tumor from normal tissues. Interaction between rs3219073, rs1805415, and rs1805414 were significantly associated with the NSCLC tumor with OR ranging from 3.61-6.75; 95%CI from 1.82 to 19.9; P-value<0.001. CONCLUSION: PARP1 haplotypes may serve as a better predictor in lung cancer development and prognosis compared to single alleles.
OBJECTIVE: The carcinogenesis role of PARP1 in lung cancer is still not clear. Analysis at allelic levels cannot fully explain the function of PARP1 on lung cancer. Our study aims to further explore the relation between PARP1 haplotypes and lung cancer. MATERIALS AND METHODS: DNA and RNA were extracted from non-small cell lung cancer (NSCLC) tumor and adjacent normal fresh frozen tissue. Five PARP1-SNPs were genotyped and PARP1-specific SNPs were imputed using IMPUTE and SHAPEIT software. The SNPs were subjected to allelic, haplotype and SNP-SNP interaction analyses. Correlation between SNPs and mRNA/protein expressions were performed. RESULTS: SNP imputation inferred the ungenotyped SNPs and increased the power for association analysis. Tumor tissue samples are more likely to carry rs1805414 (OR = 1.85; 95% CI: 1.12-3.06; P-value: 0.017) and rs1805404 (OR = 2.74; 95%CI 1.19-6.32; P-value: 0.015) compared to normal tissues. Our study is the first study to show that haplotypes comprising of 5 SNPs on PARP1 (rs1136410, rs3219073, rs1805414, rs1805404, rs1805415) is able to differentiate the NSCLC tumor from normal tissues. Interaction between rs3219073, rs1805415, and rs1805414 were significantly associated with the NSCLC tumor with OR ranging from 3.61-6.75; 95%CI from 1.82 to 19.9; P-value<0.001. CONCLUSION:PARP1 haplotypes may serve as a better predictor in lung cancer development and prognosis compared to single alleles.