title: Association of Topoisomerase II (TOP2A) and Dual-Specificity Phosphatase 6 (DUSP6) Single Nucleotide Polymorphisms with Radiation Treatment Response and Prognosis of Lung Cancer in Han Chinese.
abstract: BACKGROUND Mutations of DNA topoisomerase II (TOP2A) are associated with chemotherapy resistance, whereas dual-specificity phosphatase 6 (DUSP6) negatively regulates members of the mitogen-activated protein (MAP) kinase superfamily to control cell proliferation. This study assessed TOP2A and DUSP6 single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) patients for association with chemoradiotherapy responses and prognosis. MATERIAL AND METHODS A total of 140 Chinese patients with histologically confirmed NSCLC were enrolled and subjected to genotyping of TOP2A rs471692 and DUSP6 rs2279574 using Taqman PCR. An independent sample t test was used to analyze differences in tumor regression after radiotherapy versus SNP risk factors. Kaplan-Meier curves analyzed overall survival, followed by the log-rank test and Cox proportional hazard models. RESULTS There were no significant associations of TOP2A rs471692 and DUSP6 rs2279574 polymorphisms or clinicopathological variables with response to chemoradiotherapy (p>0.05). Comparing overall survival of 87 patients with stage I-III NSCLC treated with radiotherapy or chemoradiotherapy to clinicopathological variables, the data showed that tumor regression, weight loss, clinical stage, and cigarette smoking were independent prognostic predictors (p=0.009, 0.043, 0.004, and 0.025, respectively). Tumor regression rate >0.34 was associated with patent survival versus tumor regression rate ≤0.34 (p=0.007). CONCLUSIONS TOP2A rs471692 and DUSP6 rs2279574 SNPs were not associated with chemoradiotherapy response, whereas tumor regression, weight loss, clinical stage, and cigarette smoking were independent prognostic predictors for these Chinese patients with NSCLC.
authors.affiliation: Department of Radiotherapy Oncology, The Fourth Hospital of China Medical University, Shenyang, Liaoning, China (mainland).|Department of Radiotherapy Oncology, Liaoning Cancer Hospital.
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, China (mainland).|Liaoning Provincial Department of Education, The Key Laboratory of Cancer Etiologic and Prevention, The First Hospital of China Medical University, Liaoning, Liaoning, China (mainland).
authors.forename: Yang-Wu
authors.initials: YW
authors.lastname: Ren
authors.affiliation: Department of Radiotherapy Oncology, The Fourth Hospital of China Medical University, Shenyang, Liaoning, China (mainland).|Department of Radiotherapy Oncology, Shenyang Chest Hospital, Shenyang, Liaoning, China (mainland).
authors.forename: He-Tong
authors.initials: HT
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy Oncology, Liaoning Cancer Hospital.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Radiotherapy Oncology, The Fourth Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D002681:China; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D054642:Dual Specificity Phosphatase 6 / Q000235:genetics* / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6; D004250:DNA Topoisomerases, Type II