Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Genetic Variants in the PI3K/PTEN/AKT/mTOR Pathway Predict Platinum-based Chemotherapy Response of Advanced Non-small Cell Lung Cancers in a Chinese Population

  • Xu, Jia-Li (Department of Oncology, The First Affiliated Hospital of Nanjing Medical University) ;
  • Wang, Zhen-Wu (Department of Radiation, Wuxi No. 4 Hospital) ;
  • Hu, Ling-Min (Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University) ;
  • Yin, Zhi-Qiang (Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University) ;
  • Huang, Ming-De (Department of Oncology, Huai'an No.1 Hospital Affiliated to Nanjing Medical University) ;
  • Hu, Zhi-Bin (Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University) ;
  • Shen, Hong-Bing (Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University) ;
  • Shu, Yong-Qian (Department of Oncology, The First Affiliated Hospital of Nanjing Medical University)
  • Published : 2012.05.30
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Abstract

Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients. Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Results: Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients. Conclusions: Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population.

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References

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