Abstract
To identify new genetic risk factors for cervical cancer, we conducted a genome-wide association study in the Han Chinese population. The initial discovery set included 1,364 individuals with cervical cancer (cases) and 3,028 female controls, and we selected a 'stringently matched samples' subset (829 cases and 990 controls) from the discovery set on the basis of principal component analysis; the follow-up stages included two independent sample sets (1,824 cases and 3,808 controls for follow-up 1 and 2,343 cases and 3,388 controls for follow-up 2). We identified strong evidence of associations between cervical cancer and two new loci: 4q12 (rs13117307, Pcombined, stringently matched = 9.69 × 10−9, per-allele odds ratio (OR)stringently matched = 1.26) and 17q12 (rs8067378, Pcombined, stringently matched = 2.00 × 10−8, per-allele ORstringently matched = 1.18). We additionally replicated an association between HLA-DPB1 and HLA-DPB2 (HLA-DPB1/2) at 6p21.32 and cervical cancer (rs4282438, Pcombined, stringently matched = 4.52 × 10−27, per-allele ORstringently matched = 0.75). Our findings provide new insights into the genetic etiology of cervical cancer.
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Acknowledgements
This study was funded by the Fund of the Key Basic Research and Development Program Foundation of China (973 Program) from the Ministry of Science and Technology of China (2009CB521808 and 2013CB911304), grants from the National Natural Science Foundation of China (81230038, 81025011, 81090414, 30973472, 81071663, 81130022, 81121001, 81230052, 81272302, 31000553, 81172464 and 81101964), Key Projects in the National Science and Technology Pillar Program during the Eleventh Five-Year Plan Period (2008BAI57B01), the High-Tech Research and Development Program of China (863 Program) (2012AA020801 and 2012AA02A515) and the Fund of the Key Laboratory of Cancer Invasion and Metastasis from Hubei Province and Tongji Hospital (HB001 and xkdy28). This work was also partially supported by the Hubei Research and Development Program (2008BCC005, 2009BCC001 and 2010BCB006), the Program for Changjiang Scholars and Innovative Research Team in University (IRT1025), the Foundation for the Author of National Excellent Doctoral Dissertation of China (201026), the Program for New Century Excellent Talents in University (NCET-09-0550) and the Shanghai Rising-Star Program (12QA1401900). We thank all participants recruited for this study. We would like to thank S. Liu, G. Wu, Z. Wang, S. Xie, S. Chen, Q. Wu, Y. Lu, B. Cao, Y. Li, Q. Chen, D. Zhu, M. Gong, S. Sun, Y. Wang, Y. Qin, R. Yang, J. Feng, T. Wang, L. Shi, J. Jiang, F. Rong, W. Zhou, M. Qian, X. Wu, X. Xia, Y. Yan, Y. Fan, M. Cao, C. Sun, Q. Ling, J. Yang, B. Zhou, Z. Zeng, L. Tang, L. Yu, Y. Han, J. Zhou, Y. Fang, P. Chen and Y. Meng for their useful help.
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D.M. took full responsibility for the study, especially in conceiving, designing and supervising the research together with Y. Shi and X.X. S.L., L. Li, Z. Hu, Shixuan Wang and J.Z. participated in the study design. D.M., S.L., X.X., L. Li, Z. Hu and Shixuan Wang supervised the diagnosis of patients and subject recruitment. Y. Shi and S.L. supervised the experiments and data analyses. Y. Shi, Zhiqiang Li, X. Li, S.L., T.H. and Z. Han performed statistical analyses, and the results were interpreted by D.M., S.L., Y. Shi and X.X. D.M., X.X., L.H., Y. Shi, L. Li, H.S., Z. Hu, J.Z., Shixuan Wang, S.L., Jihong Liu, D. Lin, C. Wu, Y.C., H. Xing, S.Z., P.Q., Y. Fan, W.D., K.S., X.S., D.W., H.D., Z. Lin, D.D., L.X., X. Cheng, W. Lv, X. Han, G.T., X.M., H.W., F.Q., L. Liu, X. Chen, Jibin Liu, J.W., Yan Shen, L.Y., Z.Y., J.Y., G.M., X. Hu, Y. Feng, H.H., Y. Jiang, Z. Lei, C.L., Y.Z., Z.W., C.Y., S.C., Yuanming Shen, S. Wu, H. Xu, C. Wang and Q.S. contributed reagents, materials and analysis tools and provided samples from different hospitals. S.L., Y. Shi, T.H., Y. Jia, Shaoshuai Wang, R.Y., Z. Hu, L.W., X. Li, K.H., Z.C., Jian Shen, Q.Z., H.Z., F.T., E.G., D. Liu, J.J., Wenjin Li, Jiawei Shen, S.P., Zhuang Li, L.Z., X. Luan, Y.W., M.C., J.C., Jihong Liu and Zheng Li performed the experiments. D.W., X.M. and H.D. provided technical support. The manuscript was drafted by S.L. and Zhiqiang Li under the supervision of D.M., Y. Shi and X.X. All authors critically reviewed the article and approved the final manuscript.
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Shi, Y., Li, L., Hu, Z. et al. A genome-wide association study identifies two new cervical cancer susceptibility loci at 4q12 and 17q12. Nat Genet 45, 918–922 (2013). https://doi.org/10.1038/ng.2687
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DOI: https://doi.org/10.1038/ng.2687
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