Polymorphism of DNA base excision repair (BER) genes affects DNA repair capacity and may alter sensitivity to platinum-based chemotherapy regimens. This study investigated polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu APE1-141T/G and XRCC1 Arg399Gln for association with clinical outcome in 235 advanced inoperable nonsmall-cell lung cancer (NSCLC) patients after treatment with platinum-based chemotherapy. The multivariate analysis showed that OGG1 326 GC was associated with poor PFS [hazard ratio (HR) 1.730, p 5 0.005], while XRCC1 399 GA, or GA1AA, was associated with poor OS in short-term period (HR 1.718, p 5 0.003; HR 1.691, p 5 0.003, respectively). Patients with OGG1 326/XRCC1 399 variant alleles had a higher risk to die early in short-term period (HR 1.929, p < 0.001). Furthermore, patients with XRCC1 399 variant allele (GA1AA) had higher risk of hematologic toxicity (p 5 0.009), whereas patients carrying the OGG1 326 variant (GG), or the APE1-141 GG variant, had reduced risk of gastrointestinal toxicity (p 5 0.015 and p 5 0.023, respectively). The data from the current study provide evidence that OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and APE1-141T/G polymorphisms may be useful in predicting clinical outcomes in patients with advanced inoperable NSCLC that will undergo platinum-based chemotherapy.Lung cancer is the leading cause of cancer-related death in the world and in China. 1 Eighty percent of lung cancer patients are diagnosed with nonsmall-cell lung cancer (NSCLC), of which nearly two thirds are diagnosed at the advanced stages (such as stage IIIB or IV), 2 making curative surgery impossible. Currently, platinum-based therapy is the major remedial option for these advanced inoperable NSCLC patients. To determine the optimal regimen for platinumbased therapy, a randomized phase III clinical trial investigated the effects of four different combinations of cisplatin or carboplatin plus paclitaxel, docetaxel or gemcitabine on 1,207 advanced NSCLC patients, and the data showed that the efficacy of each combination was similar with response rates of 30-40%. 3 The therapeutic efficacy of platinum agents is limited by drug resistance and these advanced NSCLC patients have a 5-year survival rate of only 15%. 4,5 Thus, novel approaches are urgently needed for early detection, better chemotherapeutic agents, selection of more responsive patients for the particular chemotherapy and biomarkers to predict drug sensitivity and outcome.To this end, rapid advances in genomic study have provided novel technologies and therapeutic strategies to establish individualized chemotherapy regimens, which could maximize the benefits of chemotherapy and minimize the likelihood of drug toxicity by allowing the selection of each patient for optimal drug and dosages based on the molecular profiles of their tumors. One such study has focused on DNA repair genes and their polymorphisms in patients treated with platinum-based chemotherapies. This is because DNA repair capacity in tumor cells could lead to resistance of ...