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Title: Detectable clonal mosaicism and its relationship to aging and cancer
Authors: Jacobs, K.B.
Yeager, M.
Zhou, W.
Wacholder, S.
Wang, Z.
Rodriguez-Santiago, B.
Hutchinson, A.
Deng, X.
Liu, C.
Horner, M.-J.
Cullen, M.
Epstein, C.G.
Burdett, L.
Dean, M.C.
Chatterjee, N.
Sampson, J.
Chung, C.C.
Kovaks, J.
Gapstur, S.M.
Stevens, V.L.
Teras, L.T.
Gaudet, M.M.
Albanes, D.
Weinstein, S.J.
Virtamo, J.
Taylor, P.R.
Freedman, N.D.
Abnet, C.C.
Goldstein, A.M.
Hu, N.
Yu, K.
Yuan, J.-M.
Liao, L.
Ding, T.
Qiao, Y.-L.
Gao, Y.-T.
Koh, W.-P. 
Xiang, Y.-B.
Tang, Z.-Z.
Fan, J.-H.
Aldrich, M.C.
Amos, C.
Blot, W.J.
Bock, C.H.
Gillanders, E.M.
Harris, C.C.
Haiman, C.A.
Henderson, B.E.
Kolonel, L.N.
Le Marchand, L.
McNeill, L.H.
Rybicki, B.A.
Schwartz, A.G.
Signorello, L.B.
Spitz, M.R.
Wiencke, J.K.
Wrensch, M.
Wu, X.
Zanetti, K.A.
Ziegler, R.G.
Figueroa, J.D.
Garcia-Closas, M.
Malats, N.
Marenne, G.
Prokunina-Olsson, L.
Baris, D.
Schwenn, M.
Johnson, A.
Landi, M.T.
Goldin, L.
Consonni, D.
Bertazzi, P.A.
Rotunno, M.
Rajaraman, P.
Andersson, U.
Freeman, L.E.B.
Berg, C.D.
Buring, J.E.
Butler, M.A.
Carreon, T.
Feychting, M.
Ahlbom, A.
Gaziano, J.M.
Giles, G.G.
Hallmans, G.
Hankinson, S.E.
Hartge, P.
Henriksson, R.
Inskip, P.D.
Johansen, C.
Landgren, A.
McKean-Cowdin, R.
Michaud, D.S.
Melin, B.S.
Peters, U.
Ruder, A.M.
Sesso, H.D.
Severi, G.
Shu, X.-O.
Visvanathan, K.
White, E.
Wolk, A.
Zeleniuch-Jacquotte, A.
Zheng, W.
Silverman, D.T.
Kogevinas, M.
Gonzalez, J.R.
Villa, O.
Li, D.
Duell, E.J.
Risch, H.A.
Olson, S.H.
Kooperberg, C.
Wolpin, B.M.
Jiao, L.
Hassan, M.
Wheeler, W.
Arslan, A.A.
Bueno-De-Mesquita, H.B.
Fuchs, C.S.
Gallinger, S.
Gross, M.D.
Holly, E.A.
Klein, A.P.
Lacroix, A.
Mandelson, M.T.
Petersen, G.
Boutron-Ruault, M.-C.
Bracci, P.M.
Canzian, F.
Chang, K.
Cotterchio, M.
Giovannucci, E.L.
Goggins, M.
Bolton, J.A.H.
Jenab, M.
Khaw, K.-T.
Krogh, V.
Kurtz, R.C.
McWilliams, R.R.
Mendelsohn, J.B.
Rabe, K.G.
Riboli, E.
Tjønneland, A.
Tobias, G.S.
Trichopoulos, D.
Elena, J.W.
Yu, H.
Amundadottir, L.
Stolzenberg-Solomon, R.Z.
Kraft, P.
Schumacher, F.
Stram, D.
Savage, S.A.
Mirabello, L.
Andrulis, I.L.
Wunder, J.S.
García, A.P.
Sierrasesà maga, L.
Barkauskas, D.A.
Gorlick, R.G.
Purdue, M.
Chow, W.-H.
Moore, L.E.
Schwartz, K.L.
Davis, F.G.
Hsing, A.W.
Berndt, S.I.
Black, A.
Wentzensen, N.
Brinton, L.A.
Lissowska, J.
Peplonska, B.
McGlynn, K.A.
Cook, M.B.
Graubard, B.I.
Kratz, C.P.
Greene, M.H.
Erickson, R.L.
Hunter, D.J.
Thomas, G.
Hoover, R.N.
Real, F.X.
Fraumeni Jr., J.F.
Caporaso, N.E.
Tucker, M.
Rothman, N.
Pérez-Jurado, L.A.
Chanock, S.J.
Issue Date: Jun-2012
Citation: Jacobs, K.B., Yeager, M., Zhou, W., Wacholder, S., Wang, Z., Rodriguez-Santiago, B., Hutchinson, A., Deng, X., Liu, C., Horner, M.-J., Cullen, M., Epstein, C.G., Burdett, L., Dean, M.C., Chatterjee, N., Sampson, J., Chung, C.C., Kovaks, J., Gapstur, S.M., Stevens, V.L., Teras, L.T., Gaudet, M.M., Albanes, D., Weinstein, S.J., Virtamo, J., Taylor, P.R., Freedman, N.D., Abnet, C.C., Goldstein, A.M., Hu, N., Yu, K., Yuan, J.-M., Liao, L., Ding, T., Qiao, Y.-L., Gao, Y.-T., Koh, W.-P., Xiang, Y.-B., Tang, Z.-Z., Fan, J.-H., Aldrich, M.C., Amos, C., Blot, W.J., Bock, C.H., Gillanders, E.M., Harris, C.C., Haiman, C.A., Henderson, B.E., Kolonel, L.N., Le Marchand, L., McNeill, L.H., Rybicki, B.A., Schwartz, A.G., Signorello, L.B., Spitz, M.R., Wiencke, J.K., Wrensch, M., Wu, X., Zanetti, K.A., Ziegler, R.G., Figueroa, J.D., Garcia-Closas, M., Malats, N., Marenne, G., Prokunina-Olsson, L., Baris, D., Schwenn, M., Johnson, A., Landi, M.T., Goldin, L., Consonni, D., Bertazzi, P.A., Rotunno, M., Rajaraman, P., Andersson, U., Freeman, L.E.B., Berg, C.D., Buring, J.E., Butler, M.A., Carreon, T., Feychting, M., Ahlbom, A., Gaziano, J.M., Giles, G.G., Hallmans, G., Hankinson, S.E., Hartge, P., Henriksson, R., Inskip, P.D., Johansen, C., Landgren, A., McKean-Cowdin, R., Michaud, D.S., Melin, B.S., Peters, U., Ruder, A.M., Sesso, H.D., Severi, G., Shu, X.-O., Visvanathan, K., White, E., Wolk, A., Zeleniuch-Jacquotte, A., Zheng, W., Silverman, D.T., Kogevinas, M., Gonzalez, J.R., Villa, O., Li, D., Duell, E.J., Risch, H.A., Olson, S.H., Kooperberg, C., Wolpin, B.M., Jiao, L., Hassan, M., Wheeler, W., Arslan, A.A., Bueno-De-Mesquita, H.B., Fuchs, C.S., Gallinger, S., Gross, M.D., Holly, E.A., Klein, A.P., Lacroix, A., Mandelson, M.T., Petersen, G., Boutron-Ruault, M.-C., Bracci, P.M., Canzian, F., Chang, K., Cotterchio, M., Giovannucci, E.L., Goggins, M., Bolton, J.A.H., Jenab, M., Khaw, K.-T., Krogh, V., Kurtz, R.C., McWilliams, R.R., Mendelsohn, J.B., Rabe, K.G., Riboli, E., Tjønneland, A., Tobias, G.S., Trichopoulos, D., Elena, J.W., Yu, H., Amundadottir, L., Stolzenberg-Solomon, R.Z., Kraft, P., Schumacher, F., Stram, D., Savage, S.A., Mirabello, L., Andrulis, I.L., Wunder, J.S., García, A.P., Sierrasesà maga, L., Barkauskas, D.A., Gorlick, R.G., Purdue, M., Chow, W.-H., Moore, L.E., Schwartz, K.L., Davis, F.G., Hsing, A.W., Berndt, S.I., Black, A., Wentzensen, N., Brinton, L.A., Lissowska, J., Peplonska, B., McGlynn, K.A., Cook, M.B., Graubard, B.I., Kratz, C.P., Greene, M.H., Erickson, R.L., Hunter, D.J., Thomas, G., Hoover, R.N., Real, F.X., Fraumeni Jr., J.F., Caporaso, N.E., Tucker, M., Rothman, N., Pérez-Jurado, L.A., Chanock, S.J. (2012-06). Detectable clonal mosaicism and its relationship to aging and cancer. Nature Genetics 44 (6) : 651-658. ScholarBank@NUS Repository.
Abstract: In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10 -8). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10 -11). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases. © 2012 Nature America, Inc. All rights reserved.
Source Title: Nature Genetics
ISSN: 10614036
DOI: 10.1038/ng.2270
Appears in Collections:Staff Publications

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