Gonzalez, J.R. (Juan R.)

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    Detectable clonal mosaicism and its relationship to aging and cancer
    (Nature Publishing Group, 2012-12) Johnson, A. (Alison); Goldstein, A.M. (Alisa M.); Hu, N. (Nan); Koh, W.P. (Woon-Puay); Landgren, A. (Annelie); Stevens, V.L. (Victoria L.); Wiencke, J.K. (John K.); Hunter, D.J. (David J.); Patiño-García, A. (Ana); Khaw, K.T. (Kay-Tee); Virtamo, J. (Jarmo); Schwartz, A.G. (Ann G.); Yuan, J.M. (Jian-Min); Rybicki, B.A. (Benjamin A.); Boutron-Ruault, M.C. (Marie-Christine); Wolk, A. (Alicja); Mandelson, M.T. (Margaret T.); McGlynn, K.A. (Katherine A.); Hankinson, S.E. (Susan E.); Liao, L. (Linda); Fuchs, C.S. (Charles S.); Zhou, W. (Weiyin); Erickson, R.L. (Ralph L.); Silverman, D.T. (Debra T.); Sampson, J. (Joshua); Hassan, M. (Manal); McNeill, L.H. (Lorna H.); Li, D. (Donghui); McWilliams, R.R. (Robert R.); Zheng, W. (Wei); Olson, S.H. (Sara H.); Thomas, G. (Gilles); Tang, Z.Z. (Ze-Zhong); Arslan, A.A. (Alan A.); Jenab, M. (Mazda); Elena, J.W. (Joanne W.); Rabe, K.G. (Kari G.); Villa, O. (Olaya); Wolpin, B.M. (Brian M.); Canzian, F. (Federico); Amundadottir, L. (Laufey); Qiao, Y.L. (You-Lin); Butler, M.A. (Mary A.); Cotterchio, M. (Michelle); Schwartz, K.L. (Kendra L.); Liu, C. (Chenwei); Kogevinas, M. (Manolis); Purdue, M. (Mark); Hoover, R.N. (Robert N.); Davis, F.G. (Faith G.); Johansen, C. (Christoffer); Lissowska, J. (Jolanta); Mendelsohn, J.B. (Julie B.); Hutchinson, A. (Amy); Kooperberg, C. (Charles); Marenne, G. (Gaelle); Freedman, N.D. (Neal D.); Sesso, H.D. (Howard D.); Stram, D. (Daniel); Wunder, J.S. (Jay S.); Harris, C.C. (Curtis C.); Jiao, L. (Li); Henderson, B.E. (Brian E.); Petersen, G. (Gloria); Stolzenberg-Solomon, R.Z. (Rachael Z.); Ahlbom, A. (Anders); Wentzensen, N. (Nicolas); Garcia-Closas, M. (Montserrat); Wacholder, S. (Sholom); McKean-Cowdin, R. (Roberta); Brinton, L.A. (Louise A.); Zeleniuch-Jacquotte, A. (Anne); Duell, E.J. (Eric J.); Andersson, U. (Ulrika); Beane-Freeman, L.E. (Laura E.); Kovaks, J. (Joseph); Berg, C.D. (Christine D.); Gallinger, S. (Steven); Zanetti, K.A. (Krista A.); Sierrasesumaga, L. (Luis); Blot, W.J. (William J.); Teras, L.R. (Lauren R.); Wang, Z. (Zhaoming); Fraumeni, J.F. (Joseph F.); Schwenn, M. (Molly); White, E. (Emily); Kraft, P. (Peter); Buring, J.E. (Julie E.); Giovannucci, E.L. (Edward L.); Figueroa, J.D. (Jonine D.); Albanes, D. (Demetrius); Chung, C.C. (Charles C.); Hoffman-Bolton, J.A. (Judith A.); Tobias, G.S. (Geoffrey S.); Severi, G. (Gianluca); Mirabello, L. (Lisa); Prokunina-Olsson, L. (Ludmila); Burdett, L. (Laurie); Barkauskas, D.A. (Donald A.); Feychting, M. (Maria); Haiman, C.A. (Christopher A.); Black, A. (Amanda); Michaud, D.S. (Dominique S.); Holly, E.A. (Elizabeth A.); Cook, M.B. (Michael B.); Ruder, A.M. (Avima M.); Gorlick, R.G. (Richard G.); Wrensch, M. (Margaret); Peplonska, B. (Beata); LaCroix, A. (Andrea); Weinstein, S.J. (Stephanie J.); Chow, W.H. (Wong-Ho); Gaziano, J.M. (J. Michael); Caporaso, N.E. (Neil E.); Chang, K. (Kenneth); Shu, X.O. (Xiao-Ou); Hsing, A.W. (Ann W.); Gonzalez, J.R. (Juan R.); Bock, C.H. (Cathryn H.); Real, F.X. (Francisco X.); Kratz, C.P. (Christian P.); Yu, K. (Kai); Rotunno, M. (Melissa); Gaudet, M.M. (Mia M.); Consonni, D. (Dario); Kolonel, L.N. (Laurence N.); Malats, N. (Nuria); Visvanathan, K. (Kala); Savage, S.A. (Sharon A.); Aldrich, M.C. (Melinda C.); Chanock, S.J. (Stephen J.); Bracci, P.M. (Paige M.); Rodriguez-Santiago, B. (Benjamin); Riboli, E. (Elio); Baris, D. (Dalsu); Klein, A.P. (Alison P.); Spitz, M.R. (Margaret R.); Deng, X. (Xiang); Risch, H.A. (Harvey A.); Perez-Jurado, L.A. (Luis A.); Gross, M.D. (Myron D.); Gillanders, E.M. (Elizabeth M.); Taylor, P.R. (Philip R.); Jacobs, K. (Kevin); Ding, T. (Ti); Hartge, P. (Patricia); Greene, M.H. (Mark H.); Abnet, C.C. (Christian C.); Wu, Y.Q. (Yan Q.); Peters, U. (Ulrike); Trichopoulos, D. (Dimitrios); Landi, M.T. (María Teresa); Horner, M.J. (Marie-Josephe); Le-Marchand, L. (Loic); Goldin, L. (Lynn); Gao, Y.T. (Yu-Tang); Fan, J.H. (Jin-Hu); Berndt, S.I. (Sonja I.); Epstein, C.G. (Caroline G.); Signorello, L.B. (Lisa B.); Chatterjee, N. (Nilanjan); Cullen, M. (Michael); Moore, L.E. (Lee E.); Wheeler, W. (William); Melin, B.S. (Beatrice S.); Giles, G.G. (Graham G.); Tjonneland, A. (Anne); Inskip, P.D. (Peter D.); Krogh, V. (Vittorio); Amos, C. (Christopher); Graubard, B.I. (Barry I.); Bertazzi, P.A. (Pier Alberto); Yeager, M. (Meredith); Goggins, M. (Michael); Yu, H. (Herbert); Tucker, M. (Margaret); Schumacher, F. (Fredrick); Carreon, T. (Tania); Ziegler, R.G. (Regina G.); Kurtz, R.C. (Robert C.); Henriksson, R. (Roger); Gapstur, S.M. (Susan M.); Hallmans, G. (Goran); Xiang, Y.B. (Yong-Bing); Bueno-de-Mesquita, H.B. (H. Bas); Rothman, N. (Nathaniel); Andrulis, I.L. (Irene L.); Dean, M.C. (Michael C.); Rajaraman, P. (Preetha)
    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.