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学術論文

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

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Müller-Myhsok,  Bertram
Max Planck Institute of Psychiatry, Max Planck Society;

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引用

Fehringer, G., Kraft, P., Pharoah, P. D., Eeles, R. A., Chatterjee, N., Schumacher, F. R., Schildkraut, J. M., Lindstrom, S., Brennan, P., Bickeboller, H., Houlston, R. S., Landi, M. T., Caporaso, N., Risch, A., Al Olama, A. A., Berndt, S. I., Giovannucci, E. L., Gronberg, H., Kote-Jarai, Z., Ma, J., Muir, K., Stampfer, M. J., Stevens, V. L., Wiklund, F., Willett, W. C., Goode, E. L., Permuth, J. B., Risch, H. A., Reid, B. M., Bezieau, S., Brenner, H., Chan, A. T., Chang-Claude, J., Hudson, T. J., Kocarnik, J. K., Newcomb, P. A., Schoen, R. E., Slattery, M. L., White, E., Adank, M. A., Ahsan, H., Aittomaki, K., Baglietto, L., Blomquist, C., Canzian, F., Czene, K., dos-Santos-Silva, I., Eliassen, A. H., Figueroa, J. D., Flesch-Janys, D., Fletcher, O., Garcia-Closas, M., Gaudet, M. M., Johnson, N., Hall, P., Hazra, A., Hein, R., Hofman, A., Hopper, J. L., Irwanto, A., Johansson, M., Kaaks, R., Kibriya, M. G., Lichtner, P., Liu, J., Lund, E., Makalic, E., Meindl, A., Müller-Myhsok, B., Muranen, T. A., Nevanlinna, H., Peeters, P. H., Peto, J., Prentice, R. L., Rahman, N., Sanchez, M. J., Schmidt, D. F., Schmutzler, R. K., Southey, M. C., Tamimi, R., Travis, R. C., Turnbull, C., Uitterlinden, A. G., Wang, Z., Whittemore, A. S., Yang, X. R., Zheng, W., Buchanan, D. D., Casey, G., Conti, D. V., Edlund, C. K., Gallinger, S., Haile, R. W., Jenkins, M., Le Marchand, L., Li, L., Lindor, N. M., Schmit, S. L., Thibodeau, S. N., Woods, M. O., Rafnar, T., Gudmundsson, J., Stacey, S. N., Stefansson, K., Sulem, P., Chen, Y. A., Tyrer, J. P., Christiani, D. C., Wei, Y., Shen, H., Hu, Z., Shu, X.-O., Shiraishi, K., Takahashi, A., Bosse, Y., Obeidat, M., Nickle, D., Timens, W., Freedman, M. L., Li, Q., Seminara, D., Chanock, S. J., Gong, J., Peters, U., Gruber, S. B., Amos, C. I., Sellers, T. A., Easton, D. F., Hunter, D. J., Haiman, C. A., Henderson, B. E., & Hung, R. J. (2016). Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations. CANCER RESEARCH, 76(17), 5103-5114. doi:10.1158/0008-5472.CAN-15-2980.


引用: https://hdl.handle.net/11858/00-001M-0000-002C-5963-E
要旨
Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus atCDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. (C) 2016 AACR.