Journal Article

Polymorphisms in <i>EGFR</i> and <i>VEGF</i> contribute to non-small-cell lung cancer survival in a Chinese population

Jing Dong, Juncheng Dai, Yongqian Shu, Shiyang Pan, Lin Xu, Wenping Chen, Yi Wang, Guangfu Jin, Hongxia Ma, Mingfeng Zhang, Zhibin Hu and Hongbing Shen

in Carcinogenesis

Volume 31, issue 6, pages 1080-1086
Published in print June 2010 | ISSN: 0143-3334
Published online April 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq079
Polymorphisms in EGFR and VEGF contribute to non-small-cell lung cancer survival in a Chinese population

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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.

Journal Article.  4218 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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