title: Genetic variations in radiation and chemotherapy drug action pathways and survival in locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.
abstract: OBJECTIVE
  Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC). The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy.
  
  
  METHODS
  Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR) analysis was performed to detect potential gene-gene interaction.
  
  
  RESULTS
  After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001). The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010), MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021), MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001) and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026) genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms.
  
  
  CONCLUSIONS
  Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk.
authors: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China ; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors: Huai
authors: H
authors: Liu
authors: Bin
authors: B
authors: Qi
authors: Xiang
authors: X
authors: Guo
authors: Lin-Quan
authors: LQ
authors: Tang
authors: Qiu-Yan
authors: QY
authors: Chen
authors: Lu
authors: L
authors: Zhang
authors: Ling
authors: L
authors: Guo
authors: Dong-Hua
authors: DH
authors: Luo
authors: Pei-Yu
authors: PY
authors: Huang
authors: Hao-Yuan
authors: HY
authors: Mo
authors: Yan-Qun
authors: YQ
authors: Xiang
authors: Fang
authors: F
authors: Qiu
authors: Rui
authors: R
authors: Sun
authors: Ying
authors: Y
authors: Zhang
authors: Ming-Yuan
authors: MY
authors: Chen
authors: Yi-Jun
authors: YJ
authors: Hua
authors: Xing
authors: X
authors: Lv
authors: Lin
authors: L
authors: Wang
authors: Chong
authors: C
authors: Zhao
authors: Ka-Jia
authors: KJ
authors: Cao
authors: Chao-Nan
authors: CN
authors: Qian
authors: Ming-Huang
authors: MH
authors: Hong
authors: Hai-Qiang
authors: HQ
authors: Mai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002277:Carcinoma; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy; D009363:Neoplasm Proteins / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D009363:Neoplasm Proteins