Faculty Collaboration Database

Polymorphisms in EGFR and VEGF contribute to non-small-cell lung cancer survival in a Chinese population. Carcinogenesis 2010 Jun;31(6):1080-6

Date

04/20/2010

Pubmed ID

20400478

DOI

10.1093/carcin/bgq079

Scopus ID

2-s2.0-77953937410 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

Over the last decades, combined chemotherapies that inhibit different signalling pathways together have been demonstrated to be more effective to treat the non-small-cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) and the vascular endothelium growth factor (VEGF) are two key targets. Polymorphisms in EGFR and VEGF genes have been identified to be associated with therapy-response and cancer survival. In this study, we hypothesized that single-nucleotide polymorphisms (SNPs) of EGFR and VEGF genes are associated with NSCLC patients' survival in Chinese. Therefore, we screened and genotyped 54 potentially functional SNPs as well as tagging SNPs in these two genes using Illumina Golden Gate platform in 568 NSCLC patients. We found that subjects carrying EGFR rs3735061AA and rs6958497AG/GG genotypes survived significantly shorter time [median survival time (MST): 22.2 and 19.4 months, respectively] than those carrying rs3735061AG/GG (MST: 25.1 months) and rs6958497AA (MST: 25.9 months) (log-rank P = 0.015 for rs3735061 and log-rank P = 0.028 for rs6958497). However, subjects carrying EGFR rs759165AG/AA genotypes survived significantly longer (MST: 38.7 months) than those carrying rs759165GG genotype (MST: 24.7 months) (log-rank P = 0.024). Multivariate Cox regression analyses showed that the genotypes of rs3735061AA and rs6958497AG/GG were associated with a significantly increased risk of death for NSCLC [hazard ratio (HR) = 2.82, 95% confidence interval (CI) = 1.66-4.78 for rs3735061AA and HR = 1.69, 95% CI = 1.26-2.28 for rs6958497AG/GG], whereas the rs759165AG/AA were associated with a 44% significantly decreased risk of death of NSCLC (HR = 0.56, 95% CI = 0.39-0.83). Stepwise COX regression analyses suggested that EGFR rs373506, rs759165 and rs6958497 may be independent candidate biomarkers to predict NSCLC survival in this population.

Author List

Dong J, Dai J, Shu Y, Pan S, Xu L, Chen W, Wang Y, Jin G, Ma H, Zhang M, Hu Z, Shen H

Author

Jing Dong PhD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung
China
Cohort Studies
ErbB Receptors
Female
Humans
Lung Neoplasms
Male
Middle Aged
Polymorphism, Single Nucleotide
Prognosis
Survival Rate
Vascular Endothelial Growth Factor A