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Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population

Nature Genetics volume 46, pages 1110–1114 (2014)Cite this article

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Abstract

To identify genetic markers for laryngeal squamous cell carcinoma (LSCC), we conducted a genome-wide association study (GWAS) on 993 individuals with LSCC (cases) and 1,995 cancer-free controls from Chinese populations. The most promising variants (association P < 1 × 10−5) were then replicated in 3 independent sets including 2,398 cases and 2,804 controls, among which we identified 3 new susceptibility loci at 11q12 (rs174549), 6p21 (rs2857595) and 12q24 (rs10492336). The minor alleles of each of these loci showed protective effects, with odds ratios (95% confidence intervals) of 0.73 (0.68–0.78; P = 1.00 × 10−20), 0.78 (0.72–0.84; P = 2.43 × 10−15) and 0.71 (0.65–0.77; P = 4.48 × 10−14), respectively. None of these variants showed an interaction with smoking or drinking. This is the first GWAS to our knowledge solely on LSCC, and the findings might advance understanding of the etiology of LSCC.

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Figure 1: Manhattan plot of genome-wide P values of association.
Figure 2: Regional plots of association.

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Acknowledgements

This work was funded by the Chinese Recruitment Program of Global Experts at Fudan University (to Q.W.) and the National Natural Science Foundation of China (30721001 to D. Lin).

Author information

Author notes

  1. Qingyi Wei

    Present address: Present address: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.,

  2. Qingyi Wei, Dianke Yu, Mingbo Liu and Mengyun Wang: These authors contributed equally to this work.

Authors and Affiliations

  1. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China

    Qingyi Wei & Mengyun Wang

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Qingyi Wei

  3. Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Qingyi Wei & Mengyun Wang

  4. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Dianke Yu, Jiang Chang, Lixun Wei, Ying Huang, Yaling Han, Wen Tan, Chen Wu & Dongxin Lin

  5. Department of Otolaryngology–Head and Neck Surgery, Chinese People's Liberation Army General Hospital, Beijing, China

    Mingbo Liu, Jialing Wang & Shiming Yang

  6. Department of Pathology, Provincial Hospital affiliated to Shandong University, Jinan, China

    Miaoqing Zhao

  7. Department of Otorhinolaryngology and Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

    Ming Liu & Linli Tian

  8. State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Weihua Jia

  9. Department of Epidemiology and Biostatistics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China

    Hongxia Ma, Hua Yuan, Zhibin Hu & Hongbing Shen

  10. Department of Otolaryngology–Head and Neck Surgery, Affiliated Beijing Tongren Hospital, Capital University of Medical Sciences, Beijing, China

    Jugao Fang & Demin Han

  11. Department of Otolaryngology–Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, Jinan, China

    Wei Xu

  12. Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    Kexing Chen & Hong Zheng

  13. Department of Head and Neck Surgical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Zhengang Xu & Jie Liu

  14. Department of Head and Neck Surgery, Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China

    Qinghai Ji & Duanshu Li

Authors
  1. Qingyi Wei
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  2. Dianke Yu
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Contributions

Q.W., C.W. and D. Lin were the overall principal investigators for the study who conceived the study and obtained financial support, and they were responsible for study design, oversaw the entire study, interpreted the results, and wrote parts of and synthesized the manuscript. D.Y. and M.W. performed overall project management, oversaw laboratory analyses and reviewed the manuscript. Mingbo Liu, J.W., S.Y., W.T., Z.X., J.L., J.F. and D.H. were responsible for subject recruitment and sample preparation for the Beijing samples. M.Z. and W.X. were responsible for subject recruitment and sample preparation for the Shandong samples. Ming Liu and L.T. were responsible for subject recruitment and sample preparation for the Heilongjiang samples. Q.J. and D. Li were responsible for subject recruitment and sample preparation for the Shanghai samples. H.M., H.Y., Z.H., H.S., K.C., W.J. and H.Z. provided part of the financial support and control samples. J.C., L.W., Y. Huang and Y. Han performed laboratory analysis and data collection.

Corresponding authors

Correspondence to Chen Wu or Dongxin Lin.

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Competing interests

The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Plots for genetic matching of three principal components (PCs) derived from the PC analysis of 993 cases with LSCC and 1,995 controls.

(a) PC1 versus PC2 for cases and controls, (b) PC1 versus PC3 for cases and controls and (c) PC2 versus PC3 for cases and controls. The good matching of cases to controls and the low λGC value (λ = 1.03) suggest minimal evidence of population stratification.

Supplementary Figure 2 Quantile-quantile plot of observed P values for association.

The red circles represent the distribution of P values for the association of 662,108 autosomal SNPs in 993 cases with laryngeal cancer and 1,995 controls.

Supplementary Figure 3 Genotype analysis of the 18 SNPs in the replication samples using a TaqMan genotyping platform (ABI 7900HT Real-Time PCR system, Applied Biosystems).

Representative profiles are shown for the genotype discrimination of (a) rs174549, (b) rs2857595 and (c) rs10492336.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3 and Supplementary Tables 1–11 (PDF 1326 kb)

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Wei, Q., Yu, D., Liu, M. et al. Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population. Nat Genet 46, 1110–1114 (2014). https://doi.org/10.1038/ng.3090

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