Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2013 Dec 10;8(12):e82750.
doi: 10.1371/journal.pone.0082750. eCollection 2013.

Genetic variations in radiation and chemotherapy drug action pathways and survival in locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy

Huai Liu  1 , Bin Qi, Xiang Guo, Lin-Quan Tang, Qiu-Yan Chen, Lu Zhang, Ling Guo, Dong-Hua Luo, Pei-Yu Huang, Hao-Yuan Mo, Yan-Qun Xiang, Fang Qiu, Rui Sun, Ying Zhang, Ming-Yuan Chen, Yi-Jun Hua, Xing Lv, Lin Wang, Chong Zhao, Ka-Jia Cao, Chao-Nan Qian, Ming-Huang Hong, Hai-Qiang Mai
Affiliations
Clinical Trial

Genetic variations in radiation and chemotherapy drug action pathways and survival in locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy

Huai Liu et al. PLoS One. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Kaplan-Meier curves for overall survival in patients with locoregionally advanced nasopharyngeal carcinoma treated with cisplatin- and fluorouracil-based chemoradiotherapy.
(A) Survival time based on the MPO rs2243828 TT, CT and CC genotypes. (B) Survival time based on the MDM2 rs2279744 TT, GT and GG genotypes. (C) Survival time based on the MPO rs2243828 TT and CT/CC genotypes. (D) Survival time based on the MDM2 rs2279744 TT and GT/GG genotypes.
Figure 2
Figure 2. Kaplan-Meier curves for progression-free survival in patients with locoregionally advanced nasopharyngeal carcinoma treated with cisplatin- and fluorouracil-based chemoradiotherapy.
(A) Survival time based on the ERCC1 rs3212986 CC, CA and AA genotypes. (B) Survival time based on the ERCC1 rs3212986 CC and CA/AA genotypes. (C) Survival time based on the MDM2 rs2279744 TT, GT and GG genotypes. (D) Survival time based on the MDM2 rs2279744 TT and GT/GG genotypes. (E) Survival time based on the MPO rs2243828 TT, CT and CC genotypes. (F) Survival time based on the MPO rs2243828 TT and CT/CC genotypes. (G) Survival time based on the ABCB1 rs2032582 GG, GT, TT, AG, AT and AA genotypes. (H) Survival time based on the ABCB1 rs2032582 GG/GT/TT/AG and AT/AA genotypes.
Figure 3
Figure 3. Kaplan-Meier survival curves for the three different risk groups classified by prognostic score models.
(A) Overall survival. (B) Progression-free survival.
Figure 4
Figure 4. Receiver operating characteristic curves of prognostic score models (PSMs) and overall stage.
(A) PSM and overall stage for overall survival. (B) PSM and overall stage for progression-free survival.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cao SM, Simons MJ, Qian CN (2011) The prevalence and prevention of nasopharyngeal carcinoma in China. Chin J Cancer 30: 114-119. doi:10.5732/cjc.010.10377. PubMed: 21272443. - DOI - PMC - PubMed
    1. Wee JT, Ha TC, Loong SL, Qian CN (2010) Is nasopharyngeal cancer really a "Cantonese cancer"? Chin J Cancer 29: 517-526. doi:10.5732/cjc.009.10329. PubMed: 20426903. - DOI - PubMed
    1. Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, et al. (1998) Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 16: 1310-1317. - PubMed
    1. Lee AW, Tung SY, Chua DT, Ngan RK, Chappell R et al. (2010) Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 102: 1188-1198. doi:10.1093/jnci/djq258. PubMed: 20634482. - DOI - PubMed
    1. Wee J, Tan EH, Tai BC, Wong HB, Leong SS et al. (2005) Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety. J Clin Oncol 23: 6730-6738. doi:10.1200/JCO.2005.16.790. PubMed: 16170180. - DOI - PubMed

Publication types

Substances