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Original research
Genetic variants associated with expression of TCF19 contribute to the risk of head and neck cancer in Chinese population
  1. Pei Ji1,2,
  2. Jiang Chang3,
  3. Xiaoyu Wei1,2,
  4. Xueyao Song1,2,
  5. Hua Yuan4,
  6. Linnan Gong1,2,
  7. Yuancheng Li1,2,
  8. Dongsheng Ding1,2,
  9. Erbao Zhang1,2,
  10. Caiwang Yan1,2,
  11. Meng Zhu1,2,
  12. Xiaoping Miao3,
  13. Chen Wu5,
  14. Guangfu Jin1,2,
  15. Zhibin Hu1,2,
  16. Hongbing Shen1,2,
  17. Hongxia Ma1,2
  1. 1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
  2. 2Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China
  3. 3Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China
  4. 4Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
  5. 5Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  1. Correspondence to Professor Hongxia Ma, Department of Epidemiology, Nanjing Medical University, Nanjing 211166, China; hongxiama{at}


Background Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common cancers worldwide and includes cancers arising from the oral cavity, pharynx and larynx. Genome-wide association studies have found several genetic variants related to the risk of SCCHN; however, they could only explain a small fraction of the heritability. Thus, more susceptibility loci associated with SCCHN need to be identified.

Methods An association study was conducted by genotyping 555 patients with SCCHN and 1367 controls in a Chinese population. Single-variant association analysis was conducted on 63 373 SNPs, and the promising variants were then confirmed by a two-stage validation with 1875 SCCHN cases and 4637 controls. Bioinformatics analysis and functional assays were applied to uncover the potential pathogenic mechanism of the promising variants and genes associated with SCCHN.

Results We first identified three novel genetic variants significantly associated with the risk of SCCHN (p=7.45×10−7 for rs2517611 at 6p22.1, p=1.76×10−9 for rs2524182 at 6p21.33 and p=2.17×10−10 for rs3131018 at 6p21.33). Further analysis and biochemical assays showed that rs3094187, which was in a region in high linkage disequilibrium with rs3131018, could modify TCF19 expression by regulating the binding affinity of the transcription factor SREBF1 to the promoter of TCF19. In addition, experiments revealed that the inhibition of TCF19 may affect several important pathways involved in tumourigenesis and attenuate the cell proliferation and migration of SCCHN.

Conclusion These findings offer important evidence that functional genetic variants could contribute to development of SCCHN and that TCF19 may function as a putative susceptibility gene for SCCHN.

  • genetics
  • genotype
  • nucleic acid amplification techniques
  • genetic variation

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  • PJ, JC, XW, XS and HY contributed equally.

  • Contributors HM conceived and designed the study. PJ, JC, XW, GL, MZ and YL analysed the data. XS, XW, DD, EZ and CY performed the experiments. HY, XM and CW provided access to validation data. MH, PJ, XS and XW drafted the manuscript. HS, ZH, and GJ revised the manuscript. All authors discussed the results and approved the manuscript.

  • Funding This work was supported by National Natural Science Foundation of China (81773525, 81922061, 81672678).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The project was approved by the Institutional Review Board of Nanjing Medical University, and the informed consent of the participants was exempted under the full review process (approval no. 2016173). Animal care and handling procedures were performed in accordance with the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals, and were approved by the Institutional Animal Care and Use Committee of Nanjing Medical University (approval no. IACUC-1805003).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository. Data are available on reasonable request. The data will be made available on reasonable request. RNA-seq data are deposited to the Gene Expression Omnibus (GEO) for public release on publication (GSE153354).

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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