The Association of Genetic Polymorphisms of TNFα, TNF-R1, and TNF-R2 and Lung Cancer Chemotherapy Response

• Yi Zheng

  Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China3Department ofPharmacy, The Maternal and Child Health of Hunan Province, Changsha 410078, P. R. China

• Ji-Ye Yin

  Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

• Ying Wang

  Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

• Xiang-Ping Li

  Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

• Juan Chen

  Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

• Chen-Yue Qian

  Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

• Xiao-Ke Wen

  Department ofPharmacy, The Maternal and Child Health of Hunan Province, Changsha 410078, P. R. China

• Wei Zhang

  Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

• Hong-Hao Zhou

  Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

• Zhao-Qian Liu

  Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, P. R. China

 Platinum-based therapy is commonly used for the treatment of lung cancer and has been widely accepted by clinicians, but the chemotherapy responses differ greatly among individuals. TNF/TNF-R1/R2 signal pathway can trigger the extrinsic pathway of apoptosis after DNA damage was caused by platinum-based treatment. The aim of this study was to investigate the association of TNF -308 A/G, TNF-R1 -383A>C, -609T>G and TNF-R2 +676 T>G and the response of platinum-based chemotherapy in 313 Chinese advanced-stage non-small-cell lung cancer (NSCLC) patients. MassARRAY was used to detect these four SNPs in three apoptosis-related genes. TNF -308 A/G was significantly correlated with better clinical benefit. Patients carrying A allele tended to have a favorable prognosis after treated with platinum-based chemotherapy (P=0.043, OR=0.488, 95%CI=0.244-0.979). The patients with CA genotype have significantly reduced risk of platinum resistance compared with wild-type homozygotes CC genotype (P=0.025, OR=0.447, 95% CI=0.220-0.906). No association was found in other polymorphisms. In conclusion, our data suggest that TNF-308 A/G polymorphism may serve as the indicator of platinum-based chemotherapy response in NSCLC patients.

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