scholarly journals GENETIC VARIANTS IN THE C-MYB SIGNALING PATHWAY GENES PREDICT SURVIVAL OF NON-SMALL CELL LUNG CANCER PATIENTS IN THE PLCO CANCER SCREENING TRIAL

Respirology ◽  
2018 ◽  
Vol 23 ◽  
pp. 19-20
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Genetic Variants ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Cancer Screening Trial ◽  
Screening Trial

scholarly journals Potentially functional genetic variants in the c-Myb signaling pathway genes are associated with survival of non-small cell lung cancer patients in the PLCO Cancer Screening Trial

2019 ◽  
Author(s):  
Yi Guo ◽  
Yun Feng ◽  
Hongliang Liu ◽  
Sheng Luo ◽  
Patricia G. Moorman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Genetic Variants ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cancer Screening Trial ◽  
Nsclc Patients ◽  
Cancer Tissues ◽  
Screening Trial ◽  
Mrna Expression Levels

Abstract Background The c-Myb signaling pathway plays a critical role in regulating expression of genes involved in differentiation, proliferation of cells and cell death, which are related to cancer progression and metastasis. Methods To test the hypothesis that genetic variants in the c-Myb pathway genes are associated with survival of non-small cell lung cancer (NSCLC) patients, we used genotyping data from 1,185 NSCLC patients in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial as the discovery dataset and 984 NSCLC patients in the Harvard Lung Cancer Susceptibility (HLCS) Study as the validation dataset. With genotyping data for 8587 SNPs in 83 genes of the c-Myb pathway from the PLCO dataset, we performed Cox proportional hazards regression analysis to evaluate association between each SNP and survival, and resultant significant SNPs were validated in the HLCS dataset and further evaluated for their functional relevance. Results Specifically, we found that ETS1 rs11606640 GA+AA and ZFHX3 rs62053220 CG+GG genotypes were associated with a favorable overall survival in NSCLC patients (Pdom=0.004 and 0.001, respectively) in a multivariable Cox model. These two validated SNPs were predicted by the RegulomeDB score to be potentially functional. In addition, ETS1 and ZFHX3 mRNA expression levels in lung cancer tissues were significantly lower than that in adjacent normal lung tissues (P<0.05 for both SNPs). Furthermore, the TCGA-based expression quantitative trait loci (eQTL) analysis showed that ETS1 rs11606640 genotypes were significantly associated with their corresponding mRNA expression levels in lung cancer tissues in both additive and recessive models (Padd=0.045 and Prec=0.042), but such a phenotype-genotype correlation for ZFHX3 rs62053220 genotypes was found in only a dominant model (Pdom=0.048). Conclusion We identified two potentially functional SNPs (ETS1 rs11606640 G>A and ZFHX3 rs62053220 C>G) that are associated with survival in NSCLC patients. Additional larger studies are needed to validate our findings.

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