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Predictive value of genetic variants XRCC1 rs1799782, APEX1 rs1760944, and MUTYH rs3219489 for adjuvant concurrent chemoradiotherapy outcomes in oral squamous cell carcinoma patients

The Pharmacogenomics Journal volume 20, pages 813–822 (2020)Cite this article

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Abstract

Genetic variations in DNA base excision repair (BER) genes may affect tumor sensitivity to chemotherapy and radiotherapy. Thus, we investigated the effects of single-nucleotide polymorphisms (SNPs) in key BER pathway genes on clinical outcomes in male patients who received concurrent chemoradiotherapy (CCRT). Seven SNPs from XRCC1, OGG1, APEX1, and MUTYH were genotyped using the Sequenom iPLEX MassARRAY system in samples from 319 men with advanced oral squamous cell carcinoma. The disease-free survival (DFS) rates of the MUTYH rs3219489 genotypes and those of the other genotypes differed significantly (log-rank test p = 0.027). Multivariate Cox proportional hazard analysis showed that the MUTYH rs3219489 GG genotype was associated with poor DFS (recessive model: hazard ratio [HR] = 2.01, 95% confidence interval [CI] = 1.31–3.10; p = 0.002). The CT + TT genotypes of XRCC1 rs1799782 (dominant model: HR = 0.65, 95% CI = 0.43–0.99; p = 0.044) and GG genotype of APEX1 rs1760944 (recessive model: HR = 1.64, 95% CI = 1.00–2.70; p = 0.050) were associated with overall survival (OS). Carrying the two risk genotypes, CC and GG of XRCC1 rs1799782 and APEX1 rs1760944, respectively, (HR = 2.95, 95% CI = 1.47–5.88; p = 0.002) increased mortality risk. Our findings showed that carrying the two risk genotypes of XRCC1 rs1799782 and APEX1 rs1760944 was associated with poor OS, while the GG genotype of MUTYH rs3219489 was associated with poor DFS. Patients carrying the risk genotypes may not benefit from CCRT; therefore, they will need alternative treatments.

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Fig. 1: Kaplan–Meier survival analysis and log-rank test of overall survival and disease-free survival curves for XRCC1 rs25489, XRCC1 rs1799782, APEX1 rs1760944, and MUTYH rs3219489 single-nucleotide polymorphisms in oral squamous cell carcinoma patients treated with concurrent chemoradiotherapy.

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Acknowledgements

The authors are grateful to the study participants.

Funding

Support for this study was obtained from Ministry of Science and Technology, Taiwan (MOST107-2314-B-038-071, MOST108-2314-B-038-088, and MOST106-2314-B-182-025-MY3), Health and Welfare Surcharge on Tobacco Products (MOHW109-TDU-B-212-134016), and Chang Gung Memorial Hospital (CMRPG3H0793, CMRPG3J0591, CMRPG3J0592 and CMRPB53).

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Authors and Affiliations

  1. School of Public Health, College of Public Health, Taipei Medical University, Taipei, 11031, Taiwan

    Thomas Senghore, You-Xin Chen & Chih-Ching Yeh

  2. Department of Nursing, School of Medicine and Allied Health Sciences, University of The Gambia, Independence Drive, Banjul, P. O. Box 1646, Banjul, The Gambia

    Thomas Senghore

  3. Department of Public Health, Chang Gung University, Taoyuan, 33302, Taiwan

    Huei-Tzu Chien & Shiang-Fu Huang

  4. Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Taoyuan, 33303, Taiwan

    Huei-Tzu Chien

  5. Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan

    Wen-Chang Wang

  6. Department of Otolaryngology, Chang Gung Memorial Hospital, Keelung, 20401, Taiwan

    Chi-Kuang Young

  7. Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, 33302, Taiwan

    Shiang-Fu Huang

  8. Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, 33305, Taiwan

    Shiang-Fu Huang

  9. Department of Public Health, College of Public Health, China Medical University, Taichung, 40402, Taiwan

    Chih-Ching Yeh

  10. Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, 11696, Taiwan

    Chih-Ching Yeh

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Senghore, T., Chien, HT., Wang, WC. et al. Predictive value of genetic variants XRCC1 rs1799782, APEX1 rs1760944, and MUTYH rs3219489 for adjuvant concurrent chemoradiotherapy outcomes in oral squamous cell carcinoma patients. Pharmacogenomics J 20, 813–822 (2020). https://doi.org/10.1038/s41397-020-0170-5

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