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

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.