The Pharmacogenomics Journal https://doi.org/10.1038/s41397-020-0170-5 ARTICLE Predictive value of genetic variants XRCC1 rs1799782, APEX1 rs1760944, and MUTYH rs3219489 for adjuvant concurrent chemoradiotherapy outcomes in oral squamous cell carcinoma patients Thomas Senghore 1,2 ● Huei-Tzu Chien 3,4 ● Wen-Chang Wang 5 ● You-Xin Chen 1 ● Chi-Kuang Young 6 ● Shiang-Fu Huang 3,7,8 ● Chih-Ching Yeh 1,9,10 Received: 30 May 2019 / Revised: 10 May 2020 / Accepted: 18 May 2020 © The Author(s), under exclusive licence to Springer Nature Limited 2020 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. Introduction Oral squamous cell carcinoma (OSCC), which includes tumors of the lips, tongue, and buccal cavity, is a serious public health issue contributing considerably to the global * Shiang-Fu Huang shiangfu.huang@gmail.com * Chih-Ching Yeh ccyeh@tmu.edu.tw 1 School of Public Health, College of Public Health, Taipei Medical University, Taipei 11031, Taiwan 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 3 Department of Public Health, Chang Gung University, Taoyuan 33302, Taiwan 4 Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan 5 Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan 6 Department of Otolaryngology, Chang Gung Memorial Hospital, Keelung 20401, Taiwan 7 Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan 33302, Taiwan 8 Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan 9 Department of Public Health, College of Public Health, China Medical University, Taichung 40402, Taiwan 10 Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan Supplementary information The online version of this article (https:// doi.org/10.1038/s41397-020-0170-5) contains supplementary material, which is available to authorized users. 1234567890();,: 1234567890();,: