title: Association of DNA base excision repair genes (OGG1, APE1 and XRCC1) polymorphisms with outcome to platinum-based chemotherapy in advanced nonsmall-cell lung cancer patients.
abstract: 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 = 0.005], while XRCC1 399 GA, or GA+AA, was associated with poor OS in short-term period (HR 1.718, p = 0.003; HR 1.691, p = 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 (GA+AA) had higher risk of hematologic toxicity (p = 0.009), whereas patients carrying the OGG1 326 variant (GG), or the APE1-141 GG variant, had reduced risk of gastrointestinal toxicity (p = 0.015 and p = 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.
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Peng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Shiheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Xiong
authors.forename: Yanping
authors.initials: Y
authors.lastname: Cun
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Qian
authors.forename: Mengxia
authors.initials: M
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
authors.forename: Lei
authors.initials: L
authors.lastname: Xia
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000556:secondary; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage; D045647:DNA Glycosylases / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000076105:X-ray Repair Cross Complementing Protein 1; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D043823:Taxoids; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D003841:Deoxycytidine; D000077143:Docetaxel; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine
keywords: base excision repair; chemotherapy; nonsmall-cell lung cancer; polymorphisms; toxicity