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Background and Purpose  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.    Material and 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.

plos one

Genetic Variations in Radiation and Chemotherapy Drug Action Pathways and Survival in locoregionally Advanced Nasopharyngeal Carcinoma Treated with Chemoradiotherapy