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.
Keywords:
base excision repair; chemotherapy; nonsmall-cell lung cancer; polymorphisms; toxicity.
© 2014 UICC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / genetics
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Adenocarcinoma / mortality
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Adenocarcinoma / secondary
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Adult
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Aged
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Aged, 80 and over
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Biomarkers, Tumor / genetics*
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / genetics*
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Carcinoma, Non-Small-Cell Lung / mortality
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Carcinoma, Non-Small-Cell Lung / secondary
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Carcinoma, Squamous Cell / drug therapy
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / mortality
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Carcinoma, Squamous Cell / secondary
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Case-Control Studies
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Cisplatin / administration & dosage
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DNA Glycosylases / genetics*
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DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics*
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DNA-Binding Proteins / genetics*
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Deoxycytidine / administration & dosage
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Deoxycytidine / analogs & derivatives
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Docetaxel
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Female
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Follow-Up Studies
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Gemcitabine
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Humans
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Lung Neoplasms / drug therapy
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Lung Neoplasms / genetics*
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Lung Neoplasms / mortality
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Lung Neoplasms / pathology
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Lymphatic Metastasis
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Male
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Middle Aged
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Neoplasm Staging
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Paclitaxel / administration & dosage
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Polymorphism, Single Nucleotide / genetics*
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Prognosis
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Prospective Studies
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Survival Rate
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Taxoids / administration & dosage
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X-ray Repair Cross Complementing Protein 1
Substances
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Biomarkers, Tumor
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DNA-Binding Proteins
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Taxoids
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X-ray Repair Cross Complementing Protein 1
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XRCC1 protein, human
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Deoxycytidine
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Docetaxel
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DNA Glycosylases
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oxoguanine glycosylase 1, human
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APEX1 protein, human
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DNA-(Apurinic or Apyrimidinic Site) Lyase
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Paclitaxel
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Cisplatin
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Gemcitabine