1. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China;
2. Department of Respirology and Critical Care Medicines, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China;
3. Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, P.R. China;
4. Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong Universtiy, Shanghai, P.R. China.
As a crucial cell cycle regulator and G2/M phase promotor, CCNB1 played an essential role in progression of chemotherapy related cell death. Platinum-based chemotherapy is still the first-line chemotherapy regimen for most advanced NSCLC patients. We aim to investigate the correlation of CCNB1 polymorphisms to the efficiency of platinum-based chemotherapy in Chinese advanced NSCLC patients. We enrolled 972 patients with advanced NSCLC, and extracted DNA from their peripheral blood for genotyping CCNB1 four tagSNPs which selected from the Hapmap database. We analyzed the association of CCNB1 four tagSNPs with efficiency of platinum-based chemotherapy. We found that rs2069429 and rs2069433 of CCNB1 were associated with the OS of advanced NSCLC patients. Patients with GG genotype of rs2069429 had longer OS than non-GG patients (HR=0.81, 95%CI=0.68-0.95, p=0.009); and patients with AA genotype of rs2069433 had longer OS than non-AA patients (HR=0.78, 95%CI=0.61-0.98, p=0.036). And the haplotype GAAA of CCNB1 was a putative factor in subgroup patients with clinical stage IV. The association of CCNB1 polymorphisms and toxicities after platinum-based chemotherapy was assessed. Rs2069433 and rs350104 were related with gastrointestinal toxicity of platinum-based chemotherapy. The patients with GG genotype of rs2069433 (p=0.013) and/or non-GG genotype of rs350104 (p=0.042) may have a severe gastrointestinal toxicity after chemotherapy, and then clinician may can reduce the dosage of chemotherapy agents to avoid sever toxicities in these patients. In summary, CCNB1 polymorphisms may contribute to the clinical efficiency of platinum-based chemotherapy in advanced NSCLC patients, and it is helpful for the personalized treatment.
Keywords: Platinum, Chemotherapy, CCNB1, Single nucleotide polymorphism, Lung cancer.